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Title: 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
Authors: Ferrarezi, D. A. F.
Bellili-Munoz, N.
Dubois-Laforgue, D.
Cheurfa, N.
Lanui, A.
Reis, A. F. [UNIFESP]
Le Feuvre, C.
Roussel, R.
Fumeron, F.
Timsit, J.
Marre, M.
Velho, G.
Universidade de São Paulo (USP)
Cochin Hosp
Univ Paris 05
Univ Paris Diderot
Universidade Federal de São Paulo (UNIFESP)
Hop La Pitie Salpetriere
Hop Xavier Bichat
Keywords: Coronary artery disease
Type 2 diabetes
VDR gene
Issue Date: 1-May-2013
Publisher: Masson Editeur
Citation: Diabetes & Metabolism. Moulineaux Cedex 9: Masson Editeur, v. 39, n. 3, p. 263-270, 2013.
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. (C) 2013 Published by Elsevier Masson SAS.
ISSN: 1262-3636
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