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 |
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| Institution: | 1. Inserm, Research Unit 695, 16, rue Henri-Huchard, 75018 Paris, France;2. University of São Paulo (USP), Faculty of Medicine, Laboratory of Human Nutrition and Metabolic Disease – LIM 25, Avenida Doutor Arnaldo 455, São Paulo, SP, CEP 01246-903, Brazil;3. Assistance Publique–Hôpitaux de Paris – Cochin Hospital, Department of Immunology and Diabetology, Avenue Denfert-Rochereau, 75014 Paris, France;4. Université Paris Descartes (Paris-5), UFR de Médecine, 15, rue de l’École-de-Médecine, 75006 Paris, France;5. Université Paris-Diderot, Sorbonne-Paris-Cité, UFR de Médecine, 16, rue Henri-Huchard, 75018 Paris, France;6. Federal University of São Paulo, Laboratory of Molecular Endocrinology, Rua Pedro de Toledo 910, São Paulo, SP, CEP 04039-002, Brazil;7. Assistance Publique–Hôpitaux de Paris – La Pitié Hospital, Department of Cardiology, 47-83, boulevard de l’Hôpital, 75013 Paris, France;8. Assistance Publique Hôpitaux de Paris – Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46, rue Henri-Huchard, 75018 Paris, France |
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| Abstract: | AimVitamin 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.MethodsA 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).ResultsIn 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).ConclusionThe 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. |
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