Role of vitamin D levels and vitamin D receptor polymorphisms in relation to coronary artery disease: the Indian atherosclerosis research study.

OBJECTIVE: Assessment of association between plasma vitamin D levels, vitamin D receptor (VDR) gene polymorphisms, and coronary artery disease (CAD) in a predisposed Asian Indian cohort. MATERIALS AND METHODS: Patients with angiographically proven CAD having age at onset less than 60 years for men and less than 65 years for women were recruited in the Indian Atherosclerosis Research Study and treated as cases (N=287), whereas asymptomatic healthy matched individuals were enrolled from the population, who showed normal electrocardiogram and acted as controls (N=241). Plasma [vitamin D (25-hydroxy vitamin D)] levels were measured by enzyme-linked immunosorbent assay, and five haplotype-tagging single nucleotide polymorphisms were genotyped by ABI Taqman assays. RESULTS: Mean vitamin D levels were significantly lower in patients with CAD (10.59 ng/ml) than in controls (11.82 ng/ml) (P=0.036). Vitamin D showed protective association against CAD (odds ratio: 0.54, 95% confidence interval: 0.34-0.84, P=0.007) after adjusting for conventional risk factors. Patients in the first vitamin D quartile showed 2.54 times greater risk for CAD than those in the fourth quartile. There was no significant association of VDR single nucleotide polymorphisms/haplotypes with either vitamin D or CAD. Vitamin D levels were significantly lower in vegetarians than in nonvegetarians (P=0.048) and showed inverse association with body weight (P=0.054), triglyceride (P=0.031), and body mass index (P=0.020). CONCLUSION: Low vitamin D level was associated with an enhanced risk for incident CAD. VDR genotypes did not show any association with either vitamin D levels or CAD.

Rationale, design & preliminary findings of the Indian Atherosclerosis Research Study.

AIMS & OBJECTIVES: Cardiovascular disease is highly prevalent among Asian Indians. The objective of the Indian Atherosclerosis Research Study (IARS) is to understand the molecular basis of Coronary Artery Disease (CAD) in this population. METHODS & RESULTS: Over 12,500 subjects from 2500 families and 2500 healthy matched controls will be enrolled by year 2010 in the IARS. Selection of participants will be based on stringent inclusion/exclusion criteria. Blood samples will be analyzed for various genes and biomarkers implicated in CAD by employing commercial or in-house developed assays as for indices of early vascular changes. To date, over 6053 individuals from 1644 families with associated demographics, clinical information and bio specimen have been enrolled and comprise of 2131 CAD patients with mean age, 55.02 +/- 0.19 years and 3901 unaffected relatives with mean age, 40.15 +/- 0.22 years. Over 70% of the CAD patients were males. There was significant association of diabetes, hypertension and smoking with CAD status (OR 2.43-4.75; 95% CI 2.01-5.59). Subjects with metabolic syndrome (MS) showed 3 times higher risk of CAD than the non MS group (OR 3.04; 95% CI 2.71-3.41). Preliminary analyses on various atherothrombotic genes relating to lipids, inflammation and growth have identified novel variants as well as unique haplotypes associated with CAD. Proteomic studies revealed strong heritability for plasma TG, IL6, hsCRP and HDL-c levels (h2 46%-86%; p < 0.01). Baseline levels of pro-inflammatory like CRP, sPLA2 and sTWEAK were significantly higher in patients with recurrent or new coronary event. Affected subjects had higher serum antibody titers to CMV, H. pylori and C Pneumoniae infections. Early results from non-invasive assessment of endothelial dysfunction using Periscope suggest that this method is a sensitive tool for delineation of sub clinical atherosclerosis. CONCLUSION: The clinical and molecular data will be systematically integrated to develop a refined algorithm for risk prediction in the Asian Indian population.

Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease.

Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed ignificantly across R353Q genotype (P < 0.0001). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively (P < 0.0001). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score -1.82; P = 0.002). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506-2.850) and 2.472 (95% c.i. = 1.679-3.641), espectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.