Association of polymorphisms in 9p21 region with CAD in North Indian population: replication of SNPs identified through GWAS.

Coronary artery disease (CAD) is one of the leading causes of death worldwide that is influenced by both environmental as well as genetic factors. Several recent genome-wide association studies (GWAS) have reported the association of multiple single nucleotide polymorphisms (SNPs) mainly in the 9p21 region with CAD. However, the association of these SNPs with CAD has not been rigorously tested in Indian population, which accounts for the largest incidences of CAD in the world. Herein, we genotyped six such SNPs (rs10116277, rs10757274, rs1333040, rs2383206, rs2383207 and rs1994016) identified through GWAS, in 754 individuals (311 angiography-confirmed CAD patients and 443 treadmill test controls) recruited mainly from North India to evaluate if these SNPs were associated with CAD. The minor allele frequency of these six SNPs was comparable to that reported in the respective GWAS. We found that three of these SNPs (rs10116277, rs1333040 and rs2383206) present at the locus 9p21 were significantly associated with CAD even after controlling for the confounding factors such as age, sex, body mass index, homocysteine, hypertension, diabetes, smoking, diet, etc. In conclusion, the locus 9p21 found to be significantly associated with cardiovascular diseases in the Caucasian populations seems to be also important in North Indian population.