Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study

The 9p21 chromosomal region has been associated with coronary artery disease (CAD) in many genome wide association studies (GWAS). To date no information exists regarding the rs1333039 SNP which showed the strongest association in the WTCCC GWAS with CAD risk in the Indian population. The present study attempts to replicate the findings in the Indian population. Genotyping for rs1333049 was done in 229 cases and 151 controls by allele-specific real-time assay. A higher frequency of the risk allele rs1333049C was seen in cases (0 center dot 60) as compared with controls (0 center dot 49), which associated with CAD risk both in univariate (OR=1 center dot 564, 95%CI=1 center dot 154-2 center dot 119, P=0 center dot 003) and multivariate analysis (OR=2 center dot 460, 95%CI=1 center dot 139-5 center dot 314, P=0 center dot 022). Increased frequency of the risk allele was seen in younger individuals with CAD where 40% individuals in the age group 30-55 years had the CC genotype as compared with 29 and 24 center dot 5% in the age group 56-65 years and >65 years, respectively (CC versus GG, P=0 center dot 045). Higher incidence of the CC genotype was seen in MI patients, but missed significance when compared with controls (OR=1 center dot 361, 95%CI=0 center dot 954-1 center dot 942, P=0 center dot 084). In conclusion, the rs1333049 variant is significantly associated with CAD risk and also with age of onset in the Western Indian population. However there are differences in the haplotype structure of this SNP with the neighbouring rs10757278 SNP, these differences emphasize the importance of genotyping all risk variants at this locus which could underlie the differences in risk susceptibility to CAD across populations.