Vitamin D receptor gene polymorphisms and HLA DRB1*04 interaction in saudi type 2 diabetes patients

Abstract

Objective(s): The vitamin D receptor (VDR) gene has been involved in the modulation of susceptibility to inflammatory and autoimmune conditions and could play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Susceptibility to T2DM, was very recently also suggested to associate with HLA alleles. We evaluated possible correlations between VDR polymorphisms, HLA alleles, and risk of developing T2DM. Material & Methods: Individuals part of a well characterized cohort followed in Riyadh, KSA (N=627: 368 T2DM patients and 259 healthy controls) were analyzed. Genomic DNA was extracted from blood and genotyped for the VDR gene single nucleotide polymorphisms (SNPs) of Fok-1, Taq-1, ApaI and Bsm-I. Analyses were run by allelic discrimination real time PCR. HLA genotyping was performed as well by PCR using sequence specific primers (PCR-SSP). Results: T2DM is significantly associated with the VDR Taq1 (rs731236-AG) and Bsm-I (rs1544410-T -CT) genotypes and the VDR rs1544410-T allele. Significant interactions resulting in a robust increase of the OR were detected between Taq1 and Bsm-I VDR polymorphisms and HLA DRB1*04; finally, VDR polymorphisms correlated with metabolic parameters of susceptibility to T2DM including serum cholesterol and HDL levels. Conclusion(s): VDR polymorphisms are present in T2DM and correlate with HLA DRB1*04 and metabolic parameters; our results confirm an association between T2DM and HLA and add this condition to the list of diseases that are likely modulated by an HLA/VDR interaction.