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19 results on '"Coumba, Ndiaye"'

1. Connectivites in Dermatology: A series of 290 cases in Dakar, Senegal

Author

Niare Ndour, Maodo Ndiaye, Boubacar Ahy Diatta, Coumba Ndiaye, Imane Berrada, Jade Kaddoura, Mamadou Sarr, Elisabeth Diouf, Saër Diadie, Mame Téné Ndiaye, Aminata Deh, Khadim Diop, Assane Diop, Moussa Diallo, Fatimata Ly, and Suzane Oumou Niang

Subjects
medicine.medical_specialty, integumentary system, business.industry, Organic Chemistry, Mean age, Retrospective cohort study, medicine.disease, Auto immune, Biochemistry, Dermatology, eye diseases, Pemphigus, Corticosteroid therapy, Epidemiology, Medicine, Bullous pemphigoid, skin and connective tissue diseases, business
Abstract

Introduction: The general objective was to determine the epidemiological, clinical, paraclinical, therapeutic and evolutionary aspects of connectivitis in the dermatology department of the CHU Aristide Le Dantec. Patients and methods: This was a retrospective and descriptive study conducted in the Dermatology Department of the University Hospital Center (UHC) Aristide Le Dantec (HALD) of Dakar between January 2009 and December 2019. Their diagnoses were retained according to the international criteria validated in the course of connectivites Results: We identified 290 cases of connectivitis. Systemic scleroderma was the most frequent in 34.42% (n=94), followed by systemic lupus in 25.86% (n=75), mixed connectivities in 22,06% (n=64) and dermatomyositis in 19,32% (n=56). Cancer was associated with dermatomyositis in 11 cases and with systemic scleroderma in 3 cases. The mean age of our patients was 38.23 years. The sex ratio was 4.2 and the mean duration of evolution was 25 months. Dermatological manifestations were constant, found in all patients. In systemic lupus, they were dominated by discoid lupus lesions found in 40% and hypochromic spots (86%) in systemic scleroderma. In dermatomyositis, skin lesions were dominated by periorbital erythroedema (66.07%). Joint manifestations were found in 56.89% of cases (n= 165), muscular manifestations in 41.37% of cases (n= 120) and pleuropulmonary manifestations in 31.3% of cases (n=91). Neuropsychiatric manifestations were noted in 5.17% of cases (n=15). All our patients were treated with corticosteroid therapy and 12.06% of them had received immunosuppressive treatment, the most commonly used molecules being methotrexate (3.44%) and cyclophosphamide (8.27%). Hydroxychloroquine was prescribed in 59.31% of patients, while D-penicillamine was prescribed in 42.06% of patients, 100% of whom were treated for systemic scleroderma. The main complications encountered were infectious complications in 83 cases (28.6%). Visceral complications, a type of visceral insufficiency, were noted in 4.13% of cases. Conclusion: Our study demonstrates the frequency of connectivitis in the dermatology department. Its particularity was the predominance of systemic scleroderma over lupus which was classically the first connectivite in dermatology services. The delay in diagnosis noted is correlated with visceral attacks; hence the importance of a better knowledge of these affections for an early management.

Published
2022
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2. NOD2/CARD15 polymorphisms (P268S, IVS8+158, G908R, L1007fs, R702W) among Kuwaiti patients with Crohn's disease: A case-control study

Author

Mohammed Faisal, Wafaa Al Hashash, Yousef Alshamali, Laurent Peyrin-Biroulet, Ferdinando D'Amico, Alaa Elshafey, Hassan Abdelnaby, Talal Al-Taweel, Ahmed Fouad, Sameh Hassan, and Ndeye Coumba Ndiaye

Subjects
medicine.medical_specialty, nod2/card15, Population, RC799-869, Gastroenterology, Polymorphism (computer science), Internal medicine, Genotype, medicine, crohn's, Allele, education, Allele frequency, Crohn's disease, education.field_of_study, business.industry, Case-control study, Diseases of the digestive system. Gastroenterology, medicine.disease, digestive system diseases, Original Article, Restriction fragment length polymorphism, business, polymorphisms, kuwait
Abstract

Background: Nucleotide-binding oligomerization domain-containing two (NOD2/CARD15) gene polymorphisms are implicated in the pathogenesis of Crohn's disease (CD). Aim: To describe the allelic frequency of NOD2/CARD15 gene variants among Kuwaiti patients with CD and investigate potential genotype/phenotype associations. Methods: Adult Kuwaiti citizens with an established diagnosis of CD and healthy controls were enrolled from October 2018 to May 2020. Three common NOD2/CARD15 polymorphisms (R702W, G908R, and L1007fs) and P268S and IVS8 +158 polymorphisms were screened by polymerase chain reaction/restriction analysis length polymorphism (PCR/RFLP). Results: Ninety adult Kuwaiti patients with CD and 210 healthy subjects (as controls) were recruited. P268S, IVS8 +158, G908R, and R702W minor alleles were identified in 38.9%, 21.1%, 12.2%, and 4.4% of CD patients, respectively. NOD2/CARD15 polymorphisms coexisted in 35 healthy controls (16.7%) and 21 CD patients (23.3%). Individuals with either a single or multiple polymorphism were approximately two times more likely to have CD than those with no polymorphism. Patients with multiple polymorphisms had significantly more stricturing and penetrating disease. Conclusion: NOD2/CARD15 gene polymorphisms were significantly associated with an increased risk of disease and aggressive phenotypes among the Kuwaiti CD population.

Published
2021

3. Calorie Restriction as a New Treatment of Inflammatory Diseases

Author

Tunay Kökten, Laurent Peyrin-Biroulet, Anne-Charlotte Heba, Didier Quilliot, Franck Hansmannel, Natacha Dreumont, Ndeye Coumba Ndiaye, Djésia Arnone, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Endocrinologie - Diabète - Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hépato-gastro-entérologie [CHRU Nancy], TK was funded by grants from the Association François Aupetit (AFA) and by the French Investments for the Future Programme (PIA) project Lorraine Université d’Excellence (reference ANR-15-IDEX-04-LUE)., DA was funded by a grant from the 'Fondation pour la Recherche Médicale'(reference ECO20170637494)., IMPACT GEENAGE, and ANR-15-IDEX-0004,LUE,Isite LUE(2015)

Subjects
0301 basic medicine, autophagy, fasting, [SDV]Life Sciences [q-bio], Longevity, Calorie restriction, Medicine (miscellaneous), 030209 endocrinology & metabolism, Review, Systemic inflammation, Bioinformatics, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Humans, Medicine, Obesity, Social determinants of health, Adiposity, Sedentary lifestyle, metabolic switch, Nutrition and Dietetics, gut microbiota, business.industry, medicine.disease, 3. Good health, inflammatory disease, Malnutrition, 030104 developmental biology, endoplasmic reticulum stress, Observational study, caloric restriction, medicine.symptom, Energy Intake, business, Food Science
Abstract

International audience; Immoderate calorie intake coupled with a sedentary lifestyle are major determinants of health issues and inflammatory diseases in modern society.The balance between energy consumption and energy expenditure is critical for longevity. Excessive energy intake and adiposity cause systemicinflammation, whereas calorie restriction (CR) without malnutrition, exerts a potent anti-inflammatory effect. The objective of this review was toprovide an overview of different strategies used to reduce calorie intake, discuss physiological mechanisms by which CR might lead to improvedhealth outcomes, and summarize the present knowledge about inflammatory diseases. We discuss emerging data of observational studies andrandomized clinical trials on CR that have been shown to reduce inflammation and improve human health. Adv Nutr 2021;00:1–13.

Published
2021
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4. Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children

Author

Maria G. Stathopoulou, George V. Dedoussis, Pia Chedid, Philippe Froguel, Sophie Visvikis-Siest, Said El Shamieh, Ndeye Coumba Ndiaye, Ali Salami, Payman Shahabi, Amélie Bonnefond, Cécile Lecoeur, Sébastien Dadé, David Meyre, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Beirut Arab University [Beyrouth, Liban] (BAU), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), McMaster University [Hamilton, Ontario], Harokopio University of Athens, Imperial College London, and Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M))

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Population, Gene Expression, Adipose tissue, Blood Pressure, Single-nucleotide polymorphism, Inflammation, 030204 cardiovascular system & hematology, Overweight, Polymorphism, Single Nucleotide, White People, Childhood obesity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Obesity, Child, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Chemokine CCL20, business.industry, Biochemistry (medical), Membrane Transport Proteins, General Medicine, medicine.disease, 030104 developmental biology, Endocrinology, Blood pressure, Adipose Tissue, Leukocytes, Mononuclear, DNA, Intergenic, Female, France, medicine.symptom, business
Abstract

Background Growing evidence reports an association between inflammatory markers, obesity and blood pressure (BP). Specifically, the intergenic single nucleotide polymorphism (SNP) rs7556897T > C (MAF = 0.34) located between SLC19A3 and the CCL20 was shown to be associated with chronic inflammatory diseases. In addition, CCL20 expression was found increased in pancreatic islets of obese rodents and human pancreatic β cells under the influence of inflammation. In this study, we hypothesized that SNP rs7556897 could affect BP levels, thus providing a link between inflammation, BP and obesity. Methods BP was measured under supine position with a manual sphygmomanometer; values reported were the means of three readings. We analyzed rs7556897 in 577 normal weight and 689 obese French children. Using real-time polymerase chain reaction (PCR), we quantified CCL20 and SLC19A3 expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) of normal weight and overweight children. Results The rs7556897C allele was negatively associated with diastolic BP in normal weight children (β = −0.012 ± 0.004, p = 0.006) but positively associated in obese children (β = 2.178 ± 0.71, p = 0.002). A significant interaction between rs7556897T > C and the obesity status (obese or normal weight) was detected (β = 3.49, p = 9.79 × 10−5) for BP in a combined population analysis. CCL20 mRNA was only expressed in the adipose tissue of overweight children, and its expression levels were 10.7× higher in PBMCs of overweight children than normal weight children. Finally, CCL20 mRNA levels were positively associated with rs7556897T > C in PBMCs of 58 normal weight children (β = 0.43, p = 0.002). SLC19A3 was not expressed in PBMCs, and in adipose tissue, it showed same levels of expression in normal weight and overweight children. The gene expression results may highlight a specific involvement of CCL20 via communicating obesity/inflammation pathways that regulate BP. Conclusions Childhood obesity reverses the effect of rs7556897T > C on diastolic BP, possibly via the modulation of CCL20 expression levels.

Published
2020
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5. Characteristics of Lymphoma in Patients with Inflammatory Bowel Disease: A Systematic Review

Author

Tunay Kökten, Pierre Feugier, Ndeye Coumba Ndiaye, Silvio Danese, Catherine Thieblemont, Laurent Beaugerie, Rémi Houlgatte, Laurent Peyrin-Biroulet, Djésia Arnone, Julien Broséus, Marie Muller, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie [CHRU Nancy], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Humanitas Clinical and Research Center [Rozzano, Milan, Italy]

Subjects
medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], Population, Follicular lymphoma, Lymphoproliferative disorders, Gastroenterology, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, MALT lymphoma, General Medicine, medicine.disease, Inflammatory Bowel Diseases, Prognosis, digestive system diseases, 3. Good health, Lymphatic system, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Complication, business
Abstract

Background Lymphoma is a dreaded complication of inflammatory bowel diseases [IBD]. Knowledge about lymphoma in patients with IBD is limited to epidemiological data and the description of risk factors. We performed a systematic review to describe the clinical characteristics and prognosis of lymphoma in patients with IBD. Methods Electronic databases were searched up to June 1, 2020. All published clinical characteristics of lymphoma occurring in patients with IBD were collected. Results Eleven studies were included. A total of 589 lymphomas were described in patients with IBD. As seen in de novo lymphoma, non-Hodgkin’s lymphoma [NHL] was the most common histological subtype [83.9%]. Diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma were the most well-represented NHL in patients with IBD [30% and 13% respectively]. Two main differences were observed in comparison with de novo lymphoma: primary intestinal lymphoma [PIL] represented a large proportion of lymphoma in patients with IBD [22–75%] whereas mucosa-associated lymphoid tissue [MALT] lymphoma was under-represented. Epstein–Barr virus [EBV]-positive status was observed in a large proportion of tumours [44–75%]. Survival data of lymphoma in patients with IBD were similar to those of de novo lymphoma. Discussion This systematic review first highlights that PIL [especially DLBCL subtype] is significantly more frequent in patients with IBD and represents the most common entity. Conversely, MALT lymphoma is extremely rare in the IBD population. However, the overall quality of the evidence is low. Further studies are required to better define lymphoma characteristics in patients with IBD.

Published
2020
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6. The Relationship Between Vascular Endothelial Growth Factor Cis- and Trans-Acting Genetic Variants and Metabolic Syndrome

Author

Majid Ghayour-Mobarhan, John Victor Lamont, Bernard Herbeth, Abdoreza Varasteh, Abdollah Bahrami, Peter Fitzgerald, Marc Rancier, Amélie Bonnefond, Helena Murray, Hassan Mehrad-Majd, Amir Avan, Sophie Visvikis-Siest, Maria G. Stathopoulou, Seyed Reza Mirhafez, Ndeye Coumba Ndiaye, Mohsen Azimi-Nezhad, Gordon A. Ferns, Mashhad University of Medical Sciences, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Randox Laboratories, Brighton and Sussex Medical School (BSMS), (Grant No. 910823) from Mashhad University of Medical Sciences (MUMS) Research Council, Université de Lorraine, Nancy, and Center for Preventive Medicine of Vandoeuvre-lès-Nancy (France)

Subjects
Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, [SDV]Life Sciences [q-bio], Blood Pressure, Iran, 030204 cardiovascular system & hematology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Gene Frequency, Polymorphism (computer science), 2. Zero hunger, Anthropometry, General Medicine, Middle Aged, Metabolic syndrome, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Vascular endothelial growth factor, Phenotype, Female, Transcriptional Activation, medicine.medical_specialty, Waist, Genotype, Systole, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Diabetes Complications, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Diabetes Mellitus, medicine, Humans, Genetic Predisposition to Disease, Alleles, Triglycerides, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetic polymorphism, Triglyceride, business.industry, medicine.disease, Single nucleotide polymorphism, 030104 developmental biology, Endocrinology, Blood pressure, chemistry, business, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND:We have investigated the association between 4 cis- and trans-genetic variants (rs6921438, rs4416670, rs6993770 and rs10738760) of the vascular endothelial growth factor (VEGF) gene and metabolic syndrome (MetS) and its individual components in an Iranian population.MATERIAL & METHOD:Three hundred and thirty-six subjects were enrolled and MetS was defined according to the International-Diabetes-Federation (IDF) criteria. Genotyping was carried out in all the individuals for 4 VEGF genetic variants using an assay based on a combination of multiplex polymerase chain reaction and biochip array hybridization.RESULTS:As may be expected, patients with MetS had significantly higher levels of serum high-sensitivity C-reactive protein, waist circumference, hip circumference, body mass index, fat percentage, systolic blood pressure, diastolic blood pressure and triglyceride, whereas the high-density lipoprotein cholesterol levels were significantly lower, compared to the control group (P < 0.05). We also found that 1 of the VEGF- level associated genetic variants, rs6993770, was associated with the presence of MetS; the less common T allele at this locus was associated with an increased risk for MetS. This association remained significant after adjustment for confounding factors (P = 0.007). Individuals with MetS carrying the AT + TT genotypes had markedly higher levels of fasting blood glucose, triglyceride and systolic blood pressure (P < 0.05).CONCLUSIONS:We have found an association between the rs6993770 polymorphism and MetS. This gene variant was also associated with serum VEGF concentrations. There was also an association between this variant and the individual components of the MetS, including triglyceride, fasting blood glucose and systolic blood pressure.Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Published
2018
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7. Telomeres: New players in immune-mediated inflammatory diseases?

Author

Laurent Peyrin-Biroulet, Anne-Charlotte Heba, Simon Toupance, Ndeye Coumba Ndiaye, Anthanase Benetos, Djésia Arnone, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHRU-Nancy, Pôle 'Maladies du Vieillissement, Gérontologie et Soins Palliatif, Doctoral Fellowship from 'Reseau Lorrain des Maladies inflammatoires chroniques intestinales' MICILOR and Association des chefs de service from CHRU de Nancy to ACH. Research award 2020 from 'Societe Francophone de Nutrition Clinique et Métabolisme' SFNCM [GRANT_NUMBER: SFNCM2020] to DA. This work was supported by the French PIA project « Lorraine Université d’Excellence », reference ANR-15-IDEX-04-LUE and the Investments for the Future program under grant agreement No. ANR-15-RHU-0004., IMPACT GEENAGE, ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), and ANR-15-IDEX-0004,LUE,Isite LUE(2015)

Subjects
Immune-mediated inflammatory diseases, [SDV]Life Sciences [q-bio], Immunology, Inflammation, Biology, Bioinformatics, medicine.disease_cause, Inflammatory bowel disease, Arthritis, Rheumatoid, Uveitis, 03 medical and health sciences, 0302 clinical medicine, Chromosome instability, Psoriasis, Spondylarthritis, medicine, Humans, Immunology and Allergy, 030304 developmental biology, 0303 health sciences, Telomere, Inflammatory Bowel Diseases, medicine.disease, Dynamics, 3. Good health, Rheumatoid arthritis, medicine.symptom, 030217 neurology & neurosurgery, Oxidative stress
Abstract

International audience; Telomeres are repetitive DNA sequences located at the ends of linear chromosomes that preserve the integrity and stability of the genome. Telomere dysfunctions due to short telomeres or altered telomere structures can ultimately lead to replicative cellular senescence and chromosomal instability, both mechanisms being hallmarks of ageing. Chronic inflammation, oxidative stress and finally telomere length (TL) dynamics have been shown to be involved in various age-related non-communicable diseases (NCDs). Immune-mediated inflammatory diseases (IMIDs), including affections such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, spondyloarthritis and uveitis belong to this group of age-related NCDs. Although in recent years, we have witnessed the emergence of studies in the literature linking these IMIDs to TL dynamics, the causality between these diseases and telomere attrition is still unclear and controversial. In this review, we provide an overview of available studies on telomere dynamics and discuss the utility of TL measurements in immune-mediated inflammatory diseases.

Published
2021
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8. IL6R haplotype rs4845625*T/rs4537545*C is a risk factor for simultaneously high CRP, LDL and ApoB levels

Author

B Alizadeh, Ndeye Coumba Ndiaye, Maria G. Stathopoulou, Sophie Visvikis-Siest, A A Arguinano, S Dadé, Elnaz Naderi, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University Medical Center Groningen [Groningen] (UMCG), Service de Médecine Interne et Médecine Générale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Apolipoprotein B, [SDV]Life Sciences [q-bio], Immunology, Single-nucleotide polymorphism, VARIANTS, Polymorphism, Single Nucleotide, 03 medical and health sciences, INFLAMMATION, Internal medicine, Diabetes mellitus, Genetics, medicine, Humans, SNP, CORONARY-HEART-DISEASE, Allele, INTERLEUKIN-6 RECEPTOR GENE, TOCILIZUMAB, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Apolipoproteins B, METABOLIC SYNDROME, biology, Haplotype, C-reactive protein, Cholesterol, LDL, Middle Aged, medicine.disease, Receptors, Interleukin-6, C-REACTIVE PROTEIN, POLYMORPHISM, 3. Good health, 030104 developmental biology, Endocrinology, Haplotypes, DENSITY-LIPOPROTEIN CHOLESTEROL, biology.protein, Female, Metabolic syndrome, ASSOCIATION ANALYSES
Abstract

Interleukin 6 receptor (IL-6R), mediating IL-6's biological functions, plays an important role in different diseases such as diabetes, obesity and cardio-vascular diseases. In this study, we investigated the effects of two single nucleotide polymorphisms (SNPs), within the IL-6R loci, previously associated with C-reactive protein (CRP) and coronary heart diseases risk, and with controversial effects on lipids traits: SNP rs4845625 and SNP rs4537545. The results showed that both investigated SNPs were antagonistically related with CRP levels; the minor rs4845625*T allele was associated with increased CRP levels (P-value = 0.011), while the minor rs4537545* T allele was associated with decreased CRP levels (P-value = 0.009). Interestingly, the minor rs4845625* T allele was significantly associated with higher low-density lipoprotein cholesterol (LDL-C) and ApoB levels (P = 0.007 and P = 0.009 respectively). Haplotype analysis showed that the TC haplotype, having the minor rs4845625* T allele, was related simultaneously with increased levels of CRP, LDL-C and ApoB levels, thus could be considered as a risk factor. Our investigation detects for the first time an independent effect of rs4845625 on LDL-C and ApoB traits, explaining an important range of those traits variability (3.49 and 5.57% respectively). Our findings might be of high clinical significance in pharmacogenomics studies of tocilizumab for which IL-6R is target.

Published
2017
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9. Zinc-Alpha-2-Glycoprotein in Inflammatory Bowel Disease

Author

Seiamak Bahram, Cécile Macquin, Laurent Peyrin-Biroulet, David Moulin, Véronique Rolli, Tunay Kökten, Ndeye-Coumba Ndiaye, Jean-Yves Jouzeau, Julie Hablot, Philippe Georgel, Patrick Netter, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunorhumathologie moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, Mice Knockout, [SDV]Life Sciences [q-bio], Zn-Alpha-2-Glycoprotein, Inflammatory bowel disease, Gastroenterology, Seminal Plasma Proteins/genetics, 03 medical and health sciences, Mice, Internal medicine, medicine, Immunology and Allergy, Animals, Humans, Colitis, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, business.industry, Animal, Zinc-Alpha-2-Glycoprotein, Case-control study, Seminal Plasma Proteins, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Seminal Plasma Proteins/blood, Disease Models, Animal, 030104 developmental biology, Ulcerative/blood, Case-Control Studies, Disease Models, Colitis, Ulcerative, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2018
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10. TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice

Author

Silvia D'Alessio, Hélène Busby-Venner, Julie Hablot, Laurent Peyrin-Biroulet, David Moulin, Céline Monot, Silvio Danese, Franck Hansmannel, Tunay Kökten, Benjamin Garnier, Jean-Yves Jouzeau, Sébastien Gibot, Ndeye-Coumba Ndiaye, Sylviane Muller, Patricia Lepage, Jean-Louis Guéant, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Faculté de Médecine [Nancy], Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Humanitas Clinical and Research Institute, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Département d’Anatomie et Cytologie Pathologiques [CHRU Nancy], Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-gastro-entérologie [CHRU Nancy], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and MOULIN, David

Subjects
0301 basic medicine, DNA, Bacterial, Male, autophagy, TREM-1, Atg1, ATG5, 03 medical and health sciences, Feces, Mice, inflammatory bowel disease, Medicine, Animals, Colitis, Animal models of IBD, endoscopy, ATG16L1, innovative therapy, Mice, Knockout, business.industry, Autophagy, Dextran Sulfate, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, dysbiosis, Autophagy-related protein 13, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Triggering Receptor Expressed on Myeloid Cells-1, 3. Good health, Gastrointestinal Microbiome, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, inflammation, peptide-based therapy, Cancer research, Unfolded protein response, Unfolded Protein Response, LR12 peptide, endoplasmic reticulum stress, business, Peptides, Dysbiosis
Abstract

International audience; Background and Aims: Triggering receptor expressed on myeloid cells-1 [TREM-1] is known to amplify inflammation in several diseases. Autophagy and endoplasmic reticulum [ER] stress, which activate the unfolded protein response [UPR], are closely linked and defects in these pathways contribute to the pathogenesis of inflammatory bowel disease [IBD]. Both autophagy and UPR are deeply involved in host-microbiota interactions for the clearance of intracellular pathogens, thus contributing to dysbiosis. We investigated whether inhibition of TREM-1 would prevent aberrant inflammation by modulating autophagy and ER stress and preventing dysbiosis.Methods: An experimental mouse model of colitis was established by dextran sulphate sodium treatment. TREM-1 was inhibited, either pharmacologically by LR12 peptide or genetically with Trem-1 knock-out [KO] mice. Colon tissues and faecal pellets of control and colitic mice were used. Levels of macroautophagy, chaperone-mediated autophagy [CMA], and UPR proteins were evaluated by western blotting. The composition of the intestinal microbiota was assessed by MiSeq sequencing in both LR12-treated and KO animals.Results: We confirmed that inhibition of TREM-1 attenuates the severity of colitis clinically, endoscopically and histologically. We observed an increase in macroautophagy [ATG1/ULK-1, ATG13, ATG5, ATG16L1, and MAP1LC3-I/II] and in CMA [HSPA8 and HSP90AA1], whereas there was a decrease in the UPR [PERK, IRE-1α, and ATF-6α] protein expression levels in TREM-1 inhibited colitic mice. TREM-1 inhibition prevented dysbiosis.Conclusions: TREM-1 may represent a novel drug target for the treatment of IBD, by modulating autophagy activity and ER stress.

Published
2018
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11. Mutation N308T of protein tyrosine phosphatase SHP-2 in two Senegalese patients with Noonan syndrome

Author

M. Diallo, Coumba Ndiaye, Babacar Mbengue, Ibrahima Bara Diop, Mohamed Leye, Haby Signat e Sy, Omar Faye, Ndiaye R, and Jean Pascal Demba Diop

Subjects
musculoskeletal diseases, Genetics, congenital, hereditary, and neonatal diseases and abnormalities, education.field_of_study, animal structures, Population, Protein tyrosine phosphatase, Biology, medicine.disease, Short stature, Molecular biology, PTPN11, Exon, medicine, Noonan syndrome, Missense mutation, Tyrosine, medicine.symptom, skin and connective tissue diseases, education
Abstract

Noonan syndrome is a genetic autosomal dominant disorder characterized by facial dysmorphy, short stature, delayed puberty and congenital heart defects. The first gene implicated in this syndrome is PTPN11, encoding protein tyrosine phosphatase SHP-2. Several studies worldwide have identified missense mutations in this gene in patients with Noonan syndrome. Our objective focused on mutations screening of PTPN11 on a Senegalese population with Noonan syndrome. Six patients clinically diagnosed with Noonan syndrome were included in this study. DNA was extracted from whole blood by phenol chloroform. Mutation screening was performed by bidirectional sequencing of amplified polymerase chain reaction (PCR) products of PTPN11 exons frequently mutated in Noonan syndrome. This study identified in two patients, a c.923AEƒC mutation in exon 8, predicting Asn308Thr (N308T) on SHP-2 protein. This is the first time that this mutation is described in Noonan syndrome in Africa, while codon 308 was reported as a hot spot mutation site in other populations. Frequently reported amino acid substitutions were Asn308Asp and Asn308Ser. All these mutations affected the protein tyrosine phosphatase domain (PTP) of SHP-2 protein exerting a gain of function which would likely explain observed phenotypes in patients. Key words: Mutation, N308T, protein tyrosine phosphatise (PTP), SHP-2 protein, Noonan syndrome, Senegal.

Published
2014
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12. High Prevalence of Metabolic Syndrome in Iran in Comparison with France: What Are the Components That Explain This?

Author

Sébastien Dadé, Sophie Visvikis-Siest, Habibollah Esmaily, Mohsen Azimi-Nezhad, Gérard Siest, Ndeye Coumba Ndiaye, S.J. Hosseini, Bernard Herbeth, and Majid Ghayour-Mobarhan

Subjects
Adult, Blood Glucose, Cross-Cultural Comparison, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Blood Pressure, Iran, Body Mass Index, Sex Factors, Internal medicine, Prevalence, otorhinolaryngologic diseases, Internal Medicine, Humans, Medicine, education, Abdominal obesity, Lipoprotein cholesterol, Hypertriglyceridemia, Metabolic Syndrome, High rate, Analysis of Variance, education.field_of_study, Chi-Square Distribution, High prevalence, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Middle Aged, medicine.disease, Endocrinology, Hyperglycemia, Obesity, Abdominal, Hypertension, population characteristics, Female, France, Waist Circumference, medicine.symptom, Metabolic syndrome, Factor Analysis, Statistical, business, Biomarkers, geographic locations
Abstract

The aim of this study was to investigate the difference in the prevalence of metabolic syndrome and its components between an Iranian and a French population.The prevalence of metabolic syndrome, defined according to the Adult Treatment Panel III (ATP III), and of related abnormalities, was estimated in 1,386 French and 1,194 Iranian adults.The prevalence of metabolic syndrome was significantly higher in Iranian women (55.0%), followed by Iranian men (30.1%), than in French men (13.7%) and French women (6.6%). Iranian women were characterized by high rates of abdominal obesity (65.0%), hypertension (52.1%), hypertriglyceridemia (43.1%), and low high-density lipoprotein cholesterol (HDL-C; 92.7%). Iranian men were characterized by high rates of hypertension (48.9%), hypertriglyceridemia (42.8%), and low HDL-C (81.8%). French men had high rates of hypertension (44.7%) and mild rates of hypertriglyceridemia (28.6%) and hyperglycemia (23.9%). There was a relationship between waist circumference and the lipid components of metabolic syndrome in both countries.The main finding of this study is the high prevalence of low HDL-C concentrations in the Iranian population, especially in Iranian women, compared with French women. Explanation of this observation could help in establishing prevention strategies.

Published
2012
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13. Association of Genetic Loci With Glucose Levels in Childhood and Adolescence

Author

Nicholas J. Timpson, George Dedoussis, Beate St Pourcain, Inga Prokopenko, Neelam Hassanali, Stephen J. Sharp, Anders Grøntved, Panos Deloukas, Lawrence J. Beilin, Soren Brage, Naveed Sattar, David M. Evans, Sophie Visvikis-Siest, Ioanna Ntalla, George Davey Smith, Debbie A Lawlor, Philippe Froguel, Stephen J. Lye, Nicholas J. Wareham, Nabila Bouatia-Naji, Adam Barker, Ulf Ekelund, Nicole M. Warrington, Claudia Langenberg, Ruth J. F. Loos, Mark I. McCarthy, Cécile Lecoeur, Trevor A. Mori, Susan M. Ring, Lyle J. Palmer, Craig E. Pennell, John P. Newnham, Ndeye Coumba Ndiaye, and Stavroula Kanoni

Subjects
Blood Glucose, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Genome-wide association study, Single-nucleotide polymorphism, Biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Germinal Center Kinases, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Genetics, Humans, Child, 030304 developmental biology, Genetic association, Glucose Transporter Type 2, Homeodomain Proteins, 0303 health sciences, Framingham Risk Score, Insulin, Tumor Suppressor Proteins, Fasting, medicine.disease, 3. Good health, Cryptochromes, DNA-Binding Proteins, Repressor Proteins, Endocrinology, Genetic Loci, Meta-analysis, biology.protein, Glucose-6-Phosphatase, Trans-Activators, Female, Glucose 6-phosphatase, Adenylyl Cyclases, Genome-Wide Association Study, Transcription Factors
Abstract

OBJECTIVE To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9–16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021–0.031) for each unit increase in the score. CONCLUSIONS Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.

Published
2011

14. Metabolic syndrome-related composite factors over 5years in the STANISLAS Family Study: Genetic heritability and common environmental influences

Author

Jean-Brice Marteau, Sophie Visvikis-Siest, Gérard Siest, Hind Berrahmoune, Coumba Ndiaye, Anastasia Samara, and Bernard Herbeth

Subjects
Adult, Male, Adolescent, Shared environment, Clinical Biochemistry, Environment, Biology, Biochemistry, Body Mass Index, Fasting glucose, Young Adult, chemistry.chemical_compound, Liver enzyme, Plasma lipids, medicine, Humans, Genetic Predisposition to Disease, Longitudinal Studies, Obesity, Child, Metabolic Syndrome, Genetics, Biochemistry (medical), Genetic Variation, General Medicine, Middle Aged, Heritability, medicine.disease, Cross-Sectional Studies, Blood pressure, chemistry, Uric acid, Female, France, Metabolic syndrome
Abstract

Background We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. Methods At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. Results At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters “risk lipids” and “protective lipids”. Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: “liver enzymes”, “adiposity/blood pressure” and “inflammation”. Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. Conclusions In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits.

Published
2010
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15. Dairy product consumption, calcium intakes, and metabolic syndrome–related factors over 5 years in the STANISLAS study

Author

Ndeye Coumba Ndiaye, Gérard Siest, Sophie Visvikis-Siest, Anastasia Samara, Bernard Herbeth, Stéphanie Billod, Frédéric Fumeron, Génétique cardiovasculaire (GC), Université Henri Poincaré - Nancy 1 (UHP), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Adult, Blood Glucose, Male, 5-y Changes, Waist, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, chemistry.chemical_element, 030209 endocrinology & metabolism, Calcium, Calcium intake, Body Mass Index, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sex Factors, Medicine, Animals, Humans, Food science, Adiposity, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, business.industry, Cholesterol, Cholesterol, HDL, Middle Aged, medicine.disease, Yogurt, Metabolic syndrome, Diet, Calcium, Dietary, Blood pressure, Milk, chemistry, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cohort, Female, Waist Circumference, business, Body mass index, Cohort study, Dairy products
Abstract

Objective We assessed the associations of total dairy products; milk, yogurt, and cottage cheese; cheese; and calcium with 5-y changes in components of the metabolic syndrome. Methods Two hundred eighty-eight men and 300 women 28 to 60 y of age from the suivi temporaire annuel non invasif de la sante des lorrains assures sociaux (STANISLAS) cohort completed at baseline a 3-d dietary record. Statistics were performed using multivariate regression analysis. Results In men, no relation was found between the four dietary indices and components of the metabolic syndrome measured at baseline. Conversely, the consumption of milk, yogurt, and cottage cheese at entry was inversely associated with 5-y changes in glucose levels ( P ≤ 0.05, P ≤ 0.01 for sex interaction) and positively with 5-y changes in high-density lipoprotein cholesterol ( P ≤ 0.05). Higher calcium intakes were significantly related to a lower 5-y increase of the body mass index (BMI) and waist circumference in men ( P ≤ 0.01, P ≤ 0.05 for sex interaction). In addition, changes in diastolic blood pressure were inversely associated with the consumption of milk, yogurt, and cottage cheese only in men with a normal BMI ( P ≤ 0.05 for BMI interaction). In women, unlike men, associations were shown for some components measured at baseline: total dairy positively related to BMI and waist circumference; total dairy, milk, yogurt, and cottage cheese, and calcium were positively related to triacylglycerols and negatively to high-density lipoprotein cholesterol. However, no significant association was found for any 5-y-changes. Conclusion In men only, a higher consumption of dairy products was associated with positive changes in the metabolic profile in a 5-y period; a higher calcium consumption was associated with a lower 5-y increase of the BMI and waist circumference.

Published
2013
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16. A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

Author

Paul Elliott, M. R. Järvelin, Amélie Bonnefond, Lars Sjöström, Andrew Walley, Anita Morandi, Mario Falchi, Aimo Ruokonen, Aurélie Dechaume, Philippe Froguel, Said El Shamieh, Lena M. S. Carlsson, Sophie Visvikis-Siest, Maria G. Stathopoulou, Rosa-Maria Guéant-Rodriguez, David Meyre, Leonardo Bottolo, Bernard Herbeth, Michel Langlois, George V. Dedoussis, Yann Labrune, Nabila Bouatia-Naji, Joris R. Delanghe, Cécile Lecoeur, Claudio Maffeis, Ndeye Coumba Ndiaye, Peter Jacobson, Gérard Siest, and Medical Research Council (MRC)

Subjects
Male, PEDIGREE ANALYSIS, Epidemiology, lcsh:Medicine, Genome-wide association study, 030204 cardiovascular system & hematology, PHENOTYPE, Pediatrics, genome-wide, 0302 clinical medicine, Risk Factors, Genotype, lcsh:Science, Child, HEMOGLOBIN, 0303 health sciences, Multidisciplinary, Haptoglobin, Genomics, haptoglobin, 3. Good health, ADIPOSE-TISSUE, Infectious Diseases, Cardiovascular Diseases, Science & Technology - Other Topics, Medicine, Female, Public Health, CHRONIC HEPATITIS-C, Research Article, Adult, children, General Science & Technology, Immunology, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, INFLAMMATION, Genome Analysis Tools, Diagnostic Medicine, Diabetes mellitus, MD Multidisciplinary, medicine, Genetics, SNP, Humans, Genetic variability, Genotyping, 030304 developmental biology, Clinical Genetics, Science & Technology, Population Biology, Haptoglobins, MULTIDISCIPLINARY SCIENCES, lcsh:R, Immunity, Biology and Life Sciences, Computational Biology, Human Genetics, medicine.disease, POLYMORPHISM, PLASMA-GLUCOSE LEVELS, CARDIOVASCULAR-DISEASES, RISK-FACTORS, biology.protein, lcsh:Q, Clinical Immunology, Genome-Wide Association Study
Abstract

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far.We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (P(overall) = 8.1 × 10(-59)), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23 ± 0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (P(total cholesterol) = 0.002 and P(LDL) = 0.0008).Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact.

Published
2012
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17. Klotho KL-VS genotype is involved in blood pressure regulation

Author

Carlos Labat, Sophie Visvikis-Siest, Bernard Herbeth, Rosine Nzietchueng, Christine Masson, Ndeye Coumba Ndiaye, Said El Shamieh, Hamanou Benachour, and Athanase Benetos

Subjects
Male, medicine.medical_specialty, Genotype, Clinical Biochemistry, Genome-wide association study, Blood Pressure, Biochemistry, Polymerase Chain Reaction, Cohort Studies, Internal medicine, medicine, Humans, Allele, Klotho, Klotho Proteins, Aged, DNA Primers, Glucuronidase, Base Sequence, business.industry, Biochemistry (medical), General Medicine, Middle Aged, medicine.disease, Pulse pressure, Endocrinology, Blood pressure, Chromosomal region, Arterial stiffness, Female, business, Genome-Wide Association Study
Abstract

Genome-wide linkage analysis studies reported the importance of the long arm of chromosome 13 in systolic blood pressure regulation. Therefore, isolating a genetic variant related to this chromosomal region could be challenging. Klotho KL-VS allele is located on this chromosomal region and its relationships with cardio-vascular risk factors need extensive investigations. The aim of the present study is to examine whether the klotho KL-VS genotype is associated with cardio-vascular risk factors, more particularly hypertension, in two independent cohorts. A secondary objective was to investigate relationships with antihypertensive treatment, arterial stiffness and carotid artery parameters.A total of 1023 French individuals were genotyped for klotho KL-VS. Participants were part of the French ERA and STANISLAS cohorts. In both cohorts, klotho KL-VS/KL-VS genotype was significantly associated with lower systolic blood pressure and pulse pressure when compared to homozygous and heterozygous more frequent (WT) allele carriers (p=0.003 and p0.001 respectively). Antihypertensive treatment stratification confirmed the previous significant associations, while a significant interaction between klotho KL-VS genotype and antihypertensive treatment was also interestingly found (0.019 for p interaction).Klotho KL-VS/KL-VS genotype may be associated with decreased cardio-vascular risk and may interact with antihypertensive treatment in order to reduce blood pressure. This finding could lead to identify subgroups of hypertensive adults who might benefit antihypertensive drug therapies.

Published
2011

18. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

Author

Stephen W. Scherer, Mònica Gratacòs, Kari Stefansson, Muriel Holder, Unnur Thorsteinsdottir, Lukas Forer, Katharina M. Roetzer, Josette Lucas, Claudia Schurmann, Satu Kaksonen, Armand Valsesia, Carina Wallgren-Pettersson, Barbara Leube, Alexandra I. F. Blakemore, Alexandre Moerman, Marco Belfiore, Anne Faudet, Dominique Gaillard, Roberto Ravazzolo, Dominique Bonneau, Marjo-Riitta Järvelin, Yongguo Yu, Louis Vallée, Bénédicte Demeer, Sophie Visvikis-Siest, Frédérique Béna, Brigitte H. W. Faas, Benoit Arveiler, Georg Homuth, Charles Coutton, Bénédicte de Fréminville, Giorgio Gimelli, Xavier Estivill, Richard I. Fisher, Stefania Gimelli, Wendy Roberts, Jacques S. Beckmann, Emilie Landais, Orah S. Platt, Robin G. Walters, Gudmar Thorleifsson, Alexandre Reymond, Anna-Liisa Hartikainen, Solenn Legallic, James F. Gusella, Peter Vollenweider, Gian Paolo Ramelli, Tõnu Esko, Boris Keren, Nine V A M Knoers, Fanny Morice-Picard, Dominique Campion, Odile Boute, Evica Rajcan-Separovic, Rolph Pfundt, Nathalie Bednarek, Martine Doco-Fenzy, Suzanne M E Lewis, Gérard Didelot, Mylène Beri, Engilbert Sigurdsson, Véronique Satre, Audrey Labalme, Carola Tengstrom, Florian Kronenberg, Florence Petit, Simon Zwolinksi, Philippe Froguel, Paul Elliott, Dorothée Cailley, Christian R. Marshall, Bruno Leheup, Klaus Dieterich, Janina S. Ried, Sylvie Jaillard, Armand Bottani, Stylianos E. Antonarakis, Elisabetta Lapi, Jean-Christophe Cuvellier, Robert M. Witwicki, Gérard Waeber, Christèle Dubourg, Marion Gérard, Lachlan J. M. Coin, Magalie Barth, Anita Kloss-Brandstätter, Vincent Mooser, Cristóbal Richart, Giuseppe Merla, Bénédicte Duban-Bedu, Yiping Shen, Ants Kurg, Audrey Guilmatre, Juliane Hoyer, Susana Jiménez-Murcia, Mafalda Mucciolo, Bai-Lin Wu, Alessandra Ferrarini, Séverine Drunat, Yves Alembik, Páll Magnússon, Han G. Brunner, Maria Antonietta Mencarelli, Dominique Descamps, R. Frank Kooy, Azzedine Aboura, Valérie Layet, Sven Bergmann, Thomas Meitinger, Peter M. Kroisel, Nathalie Van der Aa, Olivier Guillin, Michèle Mathieu-Dramard, Zoltán Kutalik, Elisabeth Flori, Laurent Pasquier, André Reis, Noam D. Beckmann, Bertrand Isidor, Delphine Héron, Philippe Jonveaux, Sergi Villatoro Gomez, Ann Nordgren, José Manuel Fernández-Real, Florence Fellmann, Fernando Fernández-Aranda, Laurence Faivre, Dimitri J. Stavropoulos, Katrin Männik, Christian Gieger, Evald Saemundsen, Agnès Guichet, Jean-Marie Cuisset, R. Touraine, Laura Bernardini, Marie-Ange Delrue, Alessandra Renieri, Omar Gustafsson, Flore Zufferey, David A. Koolen, Massimiliano Rossi, Jacqueline Chrast, Ghislaine Plessis, Faida Walha, Joris Andrieux, Ellen van Binsbergen, Albert David, Catherine Vincent-Delorme, Cédric Le Caignec, Jean Chiesa, Ndeye Coumba Ndiaye, Geraldine Joly Helas, Damien Sanlaville, Anita Rauch, Louise Harewood, Mark I. McCarthy, Bridget A. Fernandez, Sébastien Jacquemont, Hreinn Stefansson, Anneke T. Vulto-van Silfhout, Zdenek Jaros, Matthias Nauck, Hans J. Grabe, Sonia Bouquillon, Mieke M. van Haelst, Andres Metspalu, Loyse Hippolyte, Patrick Callier, Bert B.A. de Vries, Francisco J. Tinahones, Nicole de Leeuw, Julia S. El-Sayed Moustafa, Claudine Rieubland, Kay D. MacDermot, Vittoria Disciglio, Henry Völzke, Caroline Rooryck, Bettina Blaumeiser, Danielle Martinet, Marie-Claude Addor, Bruno Delobel, Jacquemont, S, Reymond, A, Zufferey, F, Harewood, L, Walters, Rg, Kutalik, Z, Martinet, D, Shen, Y, Valsesia, A, Beckmann, Nd, Thorleifsson, G, Belfiore, M, Bouquillon, S, Campion, D, de Leeuw, N, de Vries, Bb, Esko, T, Fernandez, Ba, Fernández-Aranda, F, Fernández-Real, Jm, Gratacòs, M, Guilmatre, A, Hoyer, J, Jarvelin, Mr, Kooy, Rf, Kurg, A, Le Caignec, C, Männik, K, Platt, O, Sanlaville, D, Van Haelst, Mm, Villatoro Gomez, S, Walha, F, Wu, Bl, Yu, Y, Aboura, A, Addor, Mc, Alembik, Y, Antonarakis, Se, Arveiler, B, Barth, M, Bednarek, N, Béna, F, Bergmann, S, Beri, M, Bernardini, L, Blaumeiser, B, Bonneau, D, Bottani, A, Boute, O, Brunner, Hg, Cailley, D, Callier, P, Chiesa, J, Chrast, J, Coin, L, Coutton, C, Cuisset, Jm, Cuvellier, Jc, David, A, de Freminville, B, Delobel, B, Delrue, Ma, Demeer, B, Descamps, D, Didelot, G, Dieterich, K, Disciglio, V, Doco-Fenzy, M, Drunat, S, Duban-Bedu, B, Dubourg, C, El-Sayed Moustafa, J, Elliott, P, Faas, Bh, Faivre, L, Faudet, A, Fellmann, F, Ferrarini, A, Fisher, R, Flori, E, Forer, L, Gaillard, D, Gerard, M, Gieger, C, Gimelli, S, Gimelli, G, Grabe, Hj, Guichet, A, Guillin, O, Hartikainen, Al, Heron, D, Hippolyte, L, Holder, M, Homuth, G, Isidor, B, Jaillard, S, Jaros, Z, Jiménez-Murcia, S, Helas, Gj, Jonveaux, P, Kaksonen, S, Keren, B, Kloss-Brandstätter, A, Knoers, Nv, Koolen, Da, Kroisel, Pm, Kronenberg, F, Labalme, A, Landais, E, Lapi, E, Layet, V, Legallic, S, Leheup, B, Leube, B, Lewis, S, Lucas, J, Macdermot, Kd, Magnusson, P, Marshall, C, Mathieu-Dramard, M, Mccarthy, Mi, Meitinger, T, Mencarelli, Ma, Merla, G, Moerman, A, Mooser, V, Morice-Picard, F, Mucciolo, M, Nauck, M, Ndiaye, Nc, Nordgren, A, Pasquier, L, Petit, F, Pfundt, R, Plessis, G, Rajcan-Separovic, E, Ramelli, Gp, Rauch, A, Ravazzolo, R, Reis, A, Renieri, A, Richart, C, Ried, J, Rieubland, C, Roberts, W, Roetzer, Km, Rooryck, C, Rossi, M, Saemundsen, E, Satre, V, Schurmann, C, Sigurdsson, E, Stavropoulos, Dj, Stefansson, H, Tengström, C, Thorsteinsdóttir, U, Tinahones, Fj, Touraine, R, Vallée, L, van Binsbergen, E, Van der Aa, N, Vincent-Delorme, C, Visvikis-Siest, S, Vollenweider, P, Völzke, H, Vulto-van Silfhout, At, Waeber, G, Wallgren-Pettersson, C, Witwicki, Rm, Zwolinksi, S, Andrieux, J, Estivill, X, Gusella, Jf, Gustafsson, O, Metspalu, A, Scherer, Sw, Stefansson, K, Blakemore, Ai, Beckmann, J, Froguel, P, Faculteit Medische Wetenschappen/UMCG, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Department of Genomics of Common Disease, Imperial College London, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Laboratory Medicine, Boston Children's Hospital, Center for Human Genetic Research, Massachusetts General Hospital [Boston], Ludwig Institute for Cancer Research, deCODE Genetics, deCODE genetics [Reykjavik], Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Estonian Genome and Medicine, University of Tartu, Department of human genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Institute for Genetic and Metabolic Disorders, Institute of Molecular and Cell Biology, Disciplines of Genetics and Medicine, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona-Biomedical Research Institute 'Dr Josep Trueta'-CIBERobn Fisiopatología de la Obesidad y Nutrición, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of child and adolescent health, University of Oulu-Institute of Health Sciences and Biocenter Oulu-National Institute for Health and Welfare [Helsinki], Antwerp University Hospital [Edegem] (UZA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, University Medical Center [Utrecht], Institutes of Biomedical Science, Fudan University [Shanghai]-Children's Hospital, Shanghai Children's Medical Center, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Génétique médicale, Hôpitaux Universitaires de Genève (HUG), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Reims Champagne-Ardenne (URCA), Department of Molecular Genetics, Weizmann Institute of Science [Rehovot, Israël], Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Service de Génétique clinique, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Cytogénétique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-faculté de médecine-pharmacie, AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de Neuropédiatrie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Amiens-Picardie, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service de Génétique Clinique, Department of Biotechnology, Università degli Studi di Siena = University of Siena (UNISI)-Medical Genetics, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Epidemiology and Public Health, Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Department of Experimental Cardiology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Heart Failure Research Center (HFRC), CHU Pitié-Salpêtrière [AP-HP], Institute of human genetics, International Centre for Life, Division of genetic epidemiology, HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Obstetrics and Gynecology, University of Oulu-Institute of Clinical Medicine, Laboratorio di citogenetica, G. Gaslini Institute, Department of Psychiatry and Psychotherapy, Universität Greifswald - University of Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Abteilung für Kinder und Jugendheilkunde, Landesklinikum Waldviertel Zwettl, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), The Habilitation Unit of Folkhalsan, Medical University Graz, Medical Genetics Unit, Children's Hospital Anna Meyer, Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Institute of Human Genetics and Anthropology, Heinrich-Heine University Hospital Duesseldorf, Child and Family Research Institute-University of British Columbia (UBC), North West Thames Regional Genetics Service, Northwick Park & St Marks Hospital, Child and Adolescent Psychiatry, Landspitali University Hospital, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, The Wellcome Trust Centre for Human Genetics [Oxford], Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Genetics, GlaxoSmithKline R&D, GlaxoSmithKline, Institute of Clinical Chemistry and Laboratory Medicine, Génétique cardiovasculaire (GC), Université Henri Poincaré - Nancy 1 (UHP), Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Pathology, Division of pediatrics, Ospedale San Giovanni, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Department of pediatrics and CEBR, Università degli studi di Genova = University of Genoa (UniGe)-G. Gaslini Institute, Department of Internal Medicine, Universitat Rovira i Virgili-University Hospital Juan XXIII-Instituto Salud Carlos III-Ciber Fisiopatologia Obesidad y Nutricion (CIBEROBN), Division of Human Genetics, Department of Paediatrics, Inselspital-University of Bern, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, State Diagnostic, Counseling Center, University of Iceland [Reykjavik], Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Genetic Services, Rinnekoti Research Foundation, Department of Endocrinology and Nutrition, Instituto Salud Carlos III-Clinic Hospital of Virgen de la Victoria-Ciber Fisiopatologia y Nutricion (CIBEROBN), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Institute for Community Medicine, Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Leenaards Foundation Prize (SJ, DM and AR), the Jérôme Lejeune Foundation (AR), the Telethon Action Suisse Foundation (AR), the Swiss National Science Foundation (AR, JSB, SB and SEA), a SNSF Sinergia grant (SJ, DM, SB, JSB and AR), the European Commission anEUploidy Integrated Project grant 037627 (AR, SB, XE, HGB and SEA), the Ludwig Institute for Cancer Research (AV), the Swiss Institute of Bioinformatics (SB, ZK), an Imperial College Dept of Medicine PhD studentship (JSe-SM), the Comprehensive Biomedical Research Centre, Imperial College Healthcare NHS Trust, and the National Institute for Health Research (PE), the Wellcome Trust and the Medical Research Council (AIFB and PF), the Instituto de Salud Carlos III (ISCIII)-FIS, the German Mental Retardation Network funded through a grant of the German Federal Ministry of Education and Research (NGFNplus 01GS08160) to A Reis and European Union-FEDER (PI081714, PS09/01778), SAF2008-02278 (XE, MG, FFA), the Belgian National Fund for Scientific Research - Flanders (NVA, RFK), the Dutch Organisation for Health Research and Development (ZONMW grant 917-86-319) and Hersenstichting Nederland (BBAdV), grant 81000346 from the Chinese National Natural Science Foundation (YGY), the Simons Foundation Autism Research Initiative, Autism Speaks and NIH grant GM061354 (JFG), and the OENB grant 13059 (AK-B). YS holds a Young Investigator Award from the Children's Tumor Foundation and Catalyst Award from Harvard Medical School, and BLW, a Fudan Scholar Research Award from Fudan University, a grant from Chinese National '973' project on Population and Health (2010CB529601) and a grant from Science and Technology Council of Shanghai (09JC1402400). ERS and SL, recipients of the Michael Smith Foundation for Health Research Scholar award, acknowledge the CIHR MOP 74502 operational grant. EGCUT received support from the EU Centre of Excellence in Genomics and FP7 grants #201413 and #245536, from Estonian Government SF0180142s08, SF0180026s09 and SF0180027s10 (AM, KM, AK). The Helmholtz Zentrum Munich and the State of Bavaria financed KORA, also supported by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823), the German Federal Ministry of Education and Research (BMBF), and the Munich Center of Health Sciences (MC Health, LMUinnovativ). CIBEROBN and CIBERESP are initiatives of ISCIII (Spain). SWS holds the GlaxoSmithKline-Canadian Institutes of Health (CIHR) Chair in Genetics, Genomics at the University of Toronto and the Hospital for Sick Children and is supported by Genome Canada and the McLaughlin Centre. deCODE was funded in part by NIH grant MH071425 (KS), EU grant HEALTH-2007-2.2.1-10-223423 (Project PsychCNV) and EU grant IMI-JU-NewMeds., Centre de génomique intégrative, Université de Lausanne (UNIL), Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics, Memorial University of Newfoundland [St. John's], Friedrich Alexander University [Erlangen-Nürnberg], Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Weizmann Institute of Science, IRCCS Casa Sollievo della Sofferenza Hospital, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Etienne-Hôpital nord, Hôpital Saint Vincent de Paul-GHICL, Centre hospitalier de Béthune, Università degli Studi di Siena (UNISI)-Medical Genetics, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Department of Human Genetics, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Innsbruck Medical University [Austria] (IMU)-HMNC Brain Health-Molecular and Clinical Pharmacology, Czech Academy of Sciences [Prague] (ASCR), University of Oxford [Oxford], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, University of Zürich [Zürich] (UZH), Universita degli studi di Genova -G. Gaslini Institute, University of Toronto-The Hospital for Sick Children, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), De Villemeur, Hervé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland., Other departments, Reymond, Alexandre, Antonarakis, Stylianos, Sloan Bena, Frédérique, Bottani, Armand, Callier, Patrick, Gimelli, Stefania, Merla, Giuseppe, Vollenweider, Peter, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Aging, Transcription, Genetic, Adolescent, Adult, Aged, Body Height, Body Mass Index, Case-Control Studies, Child, Child, Preschool, Chromosomes, Human, Pair 16, Cohort Studies, Comparative Genomic Hybridization, Developmental Disabilities, Energy Metabolism, Europe, Female, Gene Dosage, Gene Duplication, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Head, Heterozygote, Humans, Infant, Infant, Newborn, Mental Disorders, Middle Aged, Mutation, North America, Obesity, Phenotype, RNA, Messenger, Sequence Deletion, Thinness, Young Adult, Physiology, RNA, Messenger/analysis/genetics, Genome-wide association study, HIDDEN-MARKOV MODEL, 0302 clinical medicine, Sequence Deletion/genetics, ddc:576.5, 0303 health sciences, education.field_of_study, Body Height/genetics, Genetic Predisposition to Disease/genetics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, population characteristics, Chromosomes, Human, Pair 16/genetics, Human, Locus (genetics), Gene Duplication/genetics, Article, 03 medical and health sciences, Genetic, education, SNP GENOTYPING DATA, Thinness/genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Pair 16, Case-control study, nutritional and metabolic diseases, social sciences, medicine.disease, DEPENDENT PROBE AMPLIFICATION, Human medicine, Body mass index, 030217 neurology & neurosurgery, Messenger, Obesity/genetics, FAILURE-TO-THRIVE, [SDV.GEN] Life Sciences [q-bio]/Genetics, Head/anatomy & histology, METABOLIC SYNDROME, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Genetics, Multidisciplinary, TIME QUANTITATIVE PCR, Failure to thrive, medicine.symptom, Underweight, Transcription, geographic locations, Mutation/genetics, Population, Biology, Chromosomes, 150 000 MR Techniques in Brain Function, medicine, Preschool, 030304 developmental biology, COPY NUMBER VARIATION, Mental Disorders/genetics, Energy Metabolism/genetics, RELATIVE QUANTIFICATION, Gene Dosage/genetics, Newborn, BODY-MASS INDEX, CIRCULAR BINARY SEGMENTATION, RNA, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], human activities, Developmental Disabilities/genetics
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance. Leenaards Foundation Jerome Lejeune Foundation Telethon Action Suisse Foundation Swiss National Science Foundation European Commission 037627 QLG1-CT-2000-01643 Ludwig Institute for Cancer Research Swiss Institute of Bioinformatics Imperial College Department of Medicine Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust National Institute for Health Research Wellcome Trust Medical Research Council Instituto de Salud Carlos III (ISCIII)-FIS German Mental Retardation Network German Federal Ministry of Education and Research NGFNplus 01GS08160 European Union PI081714 PS09/01778 201413 245536 info:eu-repo/grantAgreement/EC/FP7/223423 Belgian National Fund for Scientific Research, Flanders Dutch Organisation for Health Research and Development (ZON-MW) 917-86-319 Hersenstichting Nederland (B.B.A.d.V.) Chinese National Natural Science Foundation 81000346 Simons Foundation Autism Research Initiative Autism Speaks NIH GM061354 MH071425 Oesterreichische Nationalbank (OENB) 13059 Children's Tumor Foundation Harvard Medical School Fudan University Chinese National '973' project on Population and Health 2010CB529601 Science and Technology Council of Shanghai 09JC1402400 Michael Smith Foundation for Health CIHR MOP 74502 Estonian Government SF0180142s08 SF0180026s09 SF0180027s10 Helmholtz Zentrum Munich State of Bavaria German National Genome Research Network 01GS0823 German Federal Ministry of Education and Research (BMBF) Munich Center of Health Sciences (MC Health, LMUinnovativ) Genome Canada McLaughlin Centre Academy of Finland 104781 120315 129269 1114194 University Hospital Oulu Biocenter University of Oulu, Finland 75617 NHLBI 5R01HL087679-02 1RL1MH083268-01 NIH/NIMH 5R01MH63706:02 ENGAGE project Medical Research Council, UK G0500539 G0600705 Academy of Finland Biocentrum Helsinki SAF2008-02278 HEALTH-F4-2007-201413

Published
2011
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19. What Is the Contribution of Two Genetic Variants Regulating VEGF Levels to Type 2 Diabetes Risk and to Microvascular Complications?

Author

Torsten Lauritzen, Julia S. El-Sayed Moustafa, Mohsen Azimi Nezhad, Oluf Pedersen, Aurélie Dechaume, Beverley Balkau, Torben Hansen, Philippe Froguel, Sophie Visvikis-Siest, Serge Hercberg, Guillaume Charpentier, Michel Marre, Olivier Lantieri, Ronan Roussel, Samy Hadjadj, Niels Grarup, Ndeye Coumba Ndiaye, Maria G. Stathopoulou, Pierre-Jean Saulnier, Amélie Bonnefond, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d' investigation clinique-plurithématique du CHU de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Steno Diabetes Center and Hagedorn Research Institute, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Service d'endocrinologie, diabétologie et nutrition [CHU Bichat], Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut inter-Régional pour la SAnté (IRSA), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Research Unit for General Practice, Aarhus, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Genomics of Common Disease, Imperial College London, Service d'Endocrinologie et de Diabétologie [Corbeil-Essonne], Hôpital de Corbeil-ESsonnes, Service Endocrinologie [CHU Poitiers], Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), BioIntelligence project, French minister of health (PHRC-Poitiers), French minister of health (PHRC-IR), AFD (Research Grant), GEMMS (Groupe d'Etude des Maladies Metaboliques et Systemiques [Poitiers, France]), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), UL, IGEPCV, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)

Subjects
Male, Vascular Endothelial Growth Factor A, Oncology, Heredity, Epidemiology, lcsh:Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, Polymerase Chain Reaction, Diabetic nephropathy, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Risk Factors, Diabetic Nephropathies, Longitudinal Studies, lcsh:Science, 0303 health sciences, education.field_of_study, Multidisciplinary, Diabetic retinopathy, Middle Aged, 3. Good health, Vascular endothelial growth factor, Medicine, Female, Research Article, Retinopathy, medicine.medical_specialty, Genotype, Clinical Research Design, Population, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Polymorphism, Single Nucleotide, Diabetes Complications, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Genetics, Genome-Wide Association Studies, medicine, Humans, Genetic Predisposition to Disease, education, Biology, Genetic Association Studies, 030304 developmental biology, Hemoglobin A, Glycosylated, Glycated Hemoglobin, Diabetic Endocrinology, Evolutionary Biology, Diabetic Retinopathy, Quantitative Traits, Population Biology, Complex Traits, business.industry, lcsh:R, Computational Biology, Human Genetics, Diabetes Mellitus Type 2, medicine.disease, Diabetes Mellitus, Type 2, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, chemistry, Case-Control Studies, Genetics of Disease, Genetic Polymorphism, lcsh:Q, Glycated hemoglobin, business, Population Genetics, Genome-Wide Association Study
Abstract

International audience; Vascular endothelial growth factor (VEGF) is a key chemokine involved in tissue growth and organ repair processes, particularly angiogenesis. Elevated circulating VEGF levels are believed to play a role in type 2 diabetes (T2D) microvascular complications, especially diabetic retinopathy. Recently, a genome-wide association study identified two common single nucleotide polymorphisms (SNPs; rs6921438 and rs10738760) explaining nearly half of the variance in circulating VEGF levels. Considering the putative contribution of VEGF to T2D and its complications, we aimed to assess the effect of these VEGF-related SNPs on the risk of T2D, nephropathy and retinopathy, as well as on variation in related traits. SNPs were genotyped in several case-control studies: French and Danish T2D studies (N cases = 6,920-N controls = 3,875 and N cases = 3,561-N controls = 2,623; respectively), two French studies one for diabetic nephropathy (N cases = 1,242-N controls = 860) and the other for diabetic retinopathy (N cases = 1,336-N controls = 1,231). The effects of each SNP on quantitative traits were analyzed in a French general population-based cohort (N = 4,760) and two French T2D studies (N = 3,480). SNP associations were assessed using logistic or linear regressions. In the French population, we found an association between the G-allele of rs6921438, shown to increase circulating VEGF levels, and increased T2D risk (OR = 1.15; P = 3.7610 25). Furthermore, the same allele was associated with higher glycated hemoglobin levels (b = 0.02%; P = 9.2610 23). However, these findings were not confirmed in the Danes. Conversely, the SNP rs10738760 was not associated with T2D in the French or Danish populations. Despite having adequate statistical power, we did not find any significant effects of rs6921438 or rs10738760 on diabetic microvascular complications or the variation in related traits in T2D patients. In spite of their impact on the variance in circulating VEGF, we did not find any association between SNPs rs6921438 and rs10738760, and the risk of T2D, diabetic nephropathy or retinopathy. The link between VEGF and T2D and its complications might be indirect and more complex than expected.

Published
2013
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