Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: the DIABHYCAR prospective study

Aim. - Vitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients.Methods. - A cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 +/- 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI).Results. - in the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05-1.29; P=0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P=0.04) alleles and baseline cases of CAD. the AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02-1.28; P = 0.04). in a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P=0.009) and TaqI (P=0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03-1.73; P=0.03).Conclusion. - the haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors. (C) 2013 Published by Elsevier Masson SAS.Societe Francophone du Diabete (SFD; French Diabetes Society)Association Diabete Risque Vasculaire (ADRV; Diabetes Vascular Risk Association), FranceMinistere de l'Enseignement Superieur et de la Recherche (MESR; Ministry of Higher Education and Research), FranceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INSERM, Res Unit 695, F-75018 Paris, FranceUniv São Paulo, Fac Med, Lab Human Nutr & Metab Dis LIM, BR-01246903 São Paulo, BrazilCochin Hosp, AP HP, Dept Immunol & Diabetol, F-75014 Paris, FranceUniv Paris 05, UFR Med, F-75006 Paris, FranceUniv Paris Diderot, Sorbonne Paris Cite, UFR Med, F-75018 Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, BR-04039002 São Paulo, BrazilHop La Pitie Salpetriere, AP HP, Dept Cardiol, F-75013 Paris, FranceHop Xavier Bichat, AP HP, Dept Diabetol Endocrinol & Nutr, F-75018 Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, BR-04039002 São Paulo, BrazilCAPES: 1798-09-0Web of Scienc