Relationship between vitamin D deficiency, vitamin D receptor gene variants, and the risk of coronary artery disease among South Indians: A case-control study

Background & objectives Vitamin D deficiency (VDD) and variations in the vitamin D receptor (VDR) gene are implicated in the pathogenesis of coronary artery disease (CAD). This study investigated the association between VDD, VDR gene variants (ApaI, BsmI, FokI, and TaqI), and CAD risk among South Indians. Methods The case-control study was conducted in 250 CAD patients and 260 matched controls. Serum vitamin D levels were measured by ELISA. Genotyping for VDR ApaI (A>C, rs7975232), BsmI (A>G, rs1544410), FokI (T>C, rs2228570), and TaqI (C>T, rs731236) was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results VDD was significantly higher among CAD patients (90%) than in controls (63%). Individuals with vitamin D levels <20 ng/ml were 5.7 times more likely to have CAD when compared to those with vitamin D levels ≥ 20 ng/ml (P<0.001, OR=5.74, 95% CI=2.92-11.30). No correlation was observed between vitamin D levels and CAD risk factors, systolic and diastolic blood pressure (r=-0.105, P=0.095, r=-0.049, P=0.437), and blood glucose (r=-0.067, P=0.304). A trend for negative correlation of vitamin D levels with cholesterol (r=-0.112, P=0.094) and triglyceride levels (r=-0.133, P=0.061) was observed. The VDR TaqI variant showed significant association with reduced CAD risk in the overall analysis (Model II, OR=0.60, 95% CI=0.39-0.90, P=0.016). The FokI variant was associated with an increased risk of CAD in males (Model III, OR=5.9, 95% CI=2.09-16.85, P=0.001). However, combined analysis of VDD and VDR gene variants indicated that neither FokI 'ff' (P=0.145) nor TaqI 'tt' (P=0.138) genotypes significantly altered CAD risk in vitamin D-deficient subjects. Interpretation & conclusions The findings of this study suggested that VDD was significantly higher among the CAD patients and increases the risk of CAD by 5.7-fold.This study revealed the differing roles of VDR gene variants in CAD susceptibility and the influence of gender and other covariates.