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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.

Introduction L’importance des manifestations dermatologiques dans le diagnostic des deficits immunitaires primitifs a ete deja rapportee par certaines etudes mais exceptionnellement en Afrique subsaharienne. Le but de cette etude est de decrire les manifestations dermatologiques au cours des deficits immunitaires primitifs sur peau noire. Materiel et methodes Il s’agit d’une etude de cohorte ouverte portant sur des enfants presentant des manifestations dermatologiques suspectes de deficit immunitaire primitif a l’hopital d’Enfant Albert Royer de Dakar. Le diagnostic de deficit immunitaire primitif est basee sur la classification phenotypique de l’union internationale des societes d’immunologistes. Resultats Vingt huit patients ont ete suivi dont 18 filles et 10 garcons. L’âge moyen etait de 7 ans (extreme = 4 mois et 18 ans). L’âge de debut des symptomes etait inferieur a 3 ans dans 17 cas, entre 3 et 10 ans dans 6 cas, superieur a 10 ans dans 5 cas. La medecine traditionnelle etait le premier recours therapeutique dans 26 cas. Les manifestations dermatologiques etaient : condylomes ano-genitaux (n = 9) ; maladie de Kaposi (n = 2), epidermodysplasie verruciforme (n = 2), varicelle maligne (n = 1), molluscum contagiosum tumoral dissemine (n = 1) ; Candidose bucco-oesophagienne (n = 1) ; mycetome fongique cervico-facial (n = 1) ; becegite disseminee (n = 1) ; tuberculose scrofuloderme (n = 1) ; lupus aigu (n = 3) ; vitiligo extensif (n = 1) ; syndrome PAA ou Pyoderma-Acne-Arthrite (n = 1) ; erythrodermie (n = 1) ; acrodermatite enteropathique (n = 2) ; lymphome cutane (n = 1). Les manifestations extradermatologiques etaient : sepsis (n = 4) ; arthrite (n = 4) ; diarrhee (n = 3) ; pneumopathie infectieuse (n = 2) ; pericardite (n = 1) ; calcifications cardiaques (n = 1) ; crises convulsives (n = 1), thyroidite auto-immune (n = 1) ; alteration de l’etat general (n = 7). Cinq cas ont beneficie d’exploration pour le typage immunologique du deficit. Cette exploration a revele : 1 deficit d’expression de la classe CMHII, 1 syndrome d’hyper Ig E, 1 deficit primitif en complement C2 et 2 deficits congenitaux en zinc. Apres 3 ans de suivi regulier de la cohorte, nous avons eu 4 perdus de vue, 3 deces dont 2 par sepsis et 1 par metastase de neoplasie, 1 cas d’aggravation de molluscum contagiosum tumoral et 7 cas de recidive de condylome. Discussion Ces resultats montrent le deficit d’exploration des deficits immunitaires primitifs dans notre contexte d’exercice et la diversite des manifestations dermatologiques revelatrices. Cependant, tous les cas qui beneficie d’un typage immunologique ont ete confirme, suggerant une tres grande sensibilite des manifestations dermatologiques pour le diagnostic des deficits immunitaires primitifs. Ce constat devra etre confirme par d’autres etudes.

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.

Genome-Wide Association Studies (GWAS) on cardiovascular diseases and related quantitative traits revealed numerous genetic variants, which however have been partially replicated, probably due to the heterogeneity of the clinical phenotypes and the populations studied. Even if novel biological pathways have been identified through these studies, there is still a long way until the validation of causal variants and their use in clinical practice as factors for prevention, risk assessment and as targets for the development of new medications. GWAS methodologies should, in the following years, integrate gene–gene and gene–environment interaction analyses in a global research strategy and also involve subsequent transcriptomic and proteomic investigations. The GWAS era is very promising but it is just at the beginning.

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.