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.

Abstract

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.

• Authors: D A F Ferrarezi, N Bellili-Muñoz, D Dubois-Laforgue, N Cheurfa, A Lamri, A F Reis, C Le Feuvre, R Roussel, F Fumeron, J Timsit, M Marre, G Velho
• Journal: Diabetes & metabolism (Diabetes Metab) Vol. 39 Issue 3 Pg. 263-70 (May 2013) ISSN: 1878-1780 [Electronic] France
• PMID: 23352876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013. Published by Elsevier Masson SAS.

Chemical References

• Receptors, Calcitriol

Topics

• Aged
• Coronary Artery Disease (complications, genetics)
• Diabetes Mellitus, Type 2 (complications, genetics)
• Female
• Genetic Predisposition to Disease
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prevalence
• Prospective Studies
• Receptors, Calcitriol (genetics)
• Risk Factors