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1. Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Author

David G. Cox, Jia Zhong, Marc G. Weisskopf, Elena Colicino, Marco Sanchez-Guerra, Joel Schwartz, Diddier Prada, Andrea A. Baccarelli, Lifang Hou, Melinda C. Power, Avron Spiro, Luis A. Herrera, Pantel S. Vokonas, Department of Environmental Health, Harvard School of Public Health, Unidad de Investigación Biomédica en Cáncer, Universidad Nacional Autónoma de México (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Department of Biomedical Informatics, Universidad Nacional Autónoma de México (UNAM), Department of Epidemiology, Department of Epidemiology [Baltimore], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Department of Veterans Affairs, VA Boston Healthcare System, DP is financially supported by Consejo Nacional de Ciencia y Tecnología(CONACYT) and the Fundación México en Harvard from the program'Postdoctoral Fellowships in the Sciences at Harvard University: Mexico'.Thepresent work has been supported by a grant from the National Institute ofEnvironmental Health Sciences (NIEHS) (R01ES021733).MP is supported by a grant from the National Institute of Aging (NIA) (T32AG027668). AS was supported by a Senior Research Career Scientist award fromthe Clinical Science Research and Development Service for the US Departmentof Veterans Affairs. The US Department of Veterans Affairs (VA) Normative AgingStudy (NAS) is supported by the Cooperative Studies Program/ERIC, USDepartment of Veterans Affairs, and is a research component of theMassachusetts Veterans Epidemiology Research and Information Center(MAVERIC). Additional support to the VA Normative Aging Study was providedby the US Department of Agriculture, Agricultural Research Service (contract53-K06-510). The views expressed in this paper are those of the authors and donot necessarily represent the views of the US Department of Veterans Affairs., Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Instituto Nacional de Cancerología – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Taibi, Nadia

Subjects
Oncology, Apolipoprotein E, Gerontology, Adult, Male, medicine.medical_specialty, Aging, Genetic variants, Genotype, Cognitive decline, Neuropsychological Tests, Odds, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Apolipoproteins E, Cognition, Polymorphism (computer science), Internal medicine, medicine, Humans, MESH: APOE, Epsilon, Alleles, Haplotypes, Genotyping, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, Polymorphism, Genetic, Haplotype, Middle Aged, Psychiatry and Mental health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Psychology, Cognition Disorders, 030217 neurology & neurosurgery, APOE, Research Article
Abstract

Background APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations. Methods We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study. Results Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03). Conclusions These results suggest a beneficial effect of polymorphism rs429358 in the oldest men. Electronic supplementary material The online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.

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2. The TCF7L2rs7903146 polymorphism, dietary intakes and type 2 diabetes risk in an Algerian population

Author

Hadjira Ouhaibi-Djellouli, Leila Houti, Sarah Aïcha Lardjam-Hetraf, Xavier Hermant, Louisa Goumidi, Nadhira Saidi-Mehtar, Sounnia Mediene-Benchekor, Aline Meirhaeghe, I. Hamani-Medjaoui, Djabaria Naïma Meroufel, Houssam Boulenouar, Philippe Amouyel, Taibi, Nadia, Laboratoire de Génétique Moléculaire et Cellulaire, Université des sciences et de la Technologie d'Oran Mohamed Boudiaf [Oran] (USTO MB), Département de Biotechnologie, Faculté des Sciences de la Nature et de la Vie, Université d ’ Oran-Université d ’ Oran, Clinique Spécialisée en Orthopédie et Rééducation des Victimes des Accidents de Travail, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Droit et Santé, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Laboratoire des Systèmes d ’Information en Santé, Université d ’ Oran, and The ISOR project was funded through a collaboration agreement betweenthe Direction de la Post-Graduation et de la Recherche-Formation (DPGRF,Algeria) and the Institut National de la Santé et de la Recherche Médicale(INSERM, France). The work in France was also part-funded through otherINSERM programs. The work in Algeria was also part-funded by the AgenceThématique de Recherche en Sciences de la Santé (ATRSS) and a grant fromthe Projets Nationaux de Recherche (PNR) program, run by the AlgerianDirection Générale de la Recherche Scientifique et du DéveloppementTechnologique/Ministère de l’Enseignement Supérieur et de la RechercheScientifique (DGRSDT/MESRS).

Subjects
Adult, Male, ISOR study, Waist, endocrine system diseases, Population, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Type 2 diabetes, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Food Preferences, 0302 clinical medicine, Polymorphism (computer science), Risk Factors, Gene-diet interaction, medicine, Genetics, Humans, Genetic Predisposition to Disease, Genetics(clinical), Polymorphism, education, Genetics (clinical), Genetic Association Studies, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, Diabetes, nutritional and metabolic diseases, Odds ratio, Middle Aged, medicine.disease, Confidence interval, TCF7L2, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Algeria, Female, Transcription Factor 7-Like 2 Protein, Research Article
Abstract

International audience; BackgroundThe transcription factor 7-like 2 (TCF7L2) gene is the most significant genetic risk factor for type 2 diabetes (T2D). Association analyses were performed on participants (n¿=¿751, aged between 30 and 64) in the ISOR population-based study in the city of Oran. Dietary intakes were estimated using a weekly food frequency questionnaire.ResultsThe T allele of the rs7903146 single nucleotide polymorphism (SNP) was associated with lower body weight (p¿=¿0.02), lower BMI (p¿=¿0.009), lower waist circumference (p¿=¿0.01) and a lower waist-to-hip ratio (p¿=¿0.02). The T allele was associated with a significantly higher risk of T2D (odds ratio (OR) (95% confidence interval)¿=¿1.55 (1.09¿2.20), p¿=¿0.01) and this association was independent of BMI. When considering the T2D risk, there were nominal interactions between the rs7903146 SNP and dessert (p¿=¿0.05) and milk intakes (p¿=¿0.01). The T2D risk was greater in T allele carriers with high dessert and milk intakes (OR¿=¿2.61 (1.51-4.52), p¿=¿0.0006, and 2.46 (1.47-4.12), p¿=¿0.0006, respectively). In subjects with a high dessert intake, the T allele was also associated with higher fasting plasma glucose concentrations (4.89¿±¿0.46 mmol/L in TT subjects, 4.72¿±¿0.48 mmol/L in CT subjects and 4.78¿±¿0.51 mmol/L in CC subjects; p¿=¿0.03).ConclusionsThe T allele of the rs7903146 SNP is associated with a significantly higher risk of T2D in an Algerian population. This association was further strengthened by a high dessert intake, suggesting that gene-diet interactions increase the T2D risk.

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3. The multiple molecular facets of fragile X-associated tremor/ataxia syndrome

Author

Nicolas Charlet-Berguerand, Flora Tassone, Chantal Sellier, Karen Usdin, Veronica J. Peschansky, Chiara Pastori, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratory of Biological Modeling (NIDDK), National Institutes of Health [Bethesda] (NIH), University of Miami Leonard M. Miller School of Medicine (UMMSM), University of California [Davis] (UC Davis), University of California, Department of Psychatry and Behavioral Sciences and Center for Therapeutic Innovation, The M.I.N.D. Institute and Department of Neurology, University of California at Davis, Institut, his work was supported by INSERM (NCB),ANR and E-RARE‘CURE FXTAS’(NCB), ERC‘RNA DISEASES’(NCB), the NationalInstitute of Mental Health (grant number 5R01MH084880-05) and theIntramural Program of the National Institute of Diabetes and Digestive andKidney Diseases (NIH, DK057808-05)., Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California (UC), CHARLET BERGUERAND, NICOLAS, and Taibi, Nadia

Subjects
medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Neurology, Ataxia, Intellectual and Developmental Disabilities (IDD), Cognitive Neuroscience, [SDV]Life Sciences [q-bio], Review, Neurodegenerative, Pathology and Forensic Medicine, Rare Diseases, Genetics, medicine, 2.1 Biological and endogenous factors, Psychology, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aetiology, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Pediatric, business.industry, Neurosciences, medicine.disease, FMR1, Human genetics, Brain Disorders, nervous system diseases, [SDV] Life Sciences [q-bio], Fragile X syndrome, Orphan Drug, Fragile X Syndrome, Neurological, Pediatrics, Perinatology and Child Health, Gait Ataxia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), medicine.symptom, business, Neuroscience, Fragile X-associated tremor/ataxia syndrome
Abstract

International audience; Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset inherited neurodegenerative disorder characterized by intentional tremor, gait ataxia, autonomic dysfunction, and cognitive decline. FXTAS is caused by the presence of a long CGG repeat tract in the 5' UTR of the FMR1 gene. In contrast to Fragile X syndrome, in which the FMR1 gene harbors over 200 CGG repeats but is transcriptionally silent, the clinical features of FXTAS arise from a toxic gain of function of the elevated levels of FMR1 transcript containing the long CGG tract. However, how this RNA leads to neuronal cell dysfunction is unknown. Here, we discuss the latest advances in the current understanding of the possible molecular basis of FXTAS.

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