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

摘要

The 9p21 chromosomal region has been associated with coronary artery disease (CAD) in many genome wideassociation studies (GWAS). To date no information exists regarding the rs1333039 SNP which showed thestrongest association in the WTCCC GWAS with CAD risk in the Indian population. The present studyattempts 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 (0.60) as compared with controls (0.49),which associated with CAD risk both in univariate (OR=1.564, 95%CI=1.154–2.119, P=0.003) and multivariateanalysis (OR=2.460, 95%CI=1.139–5.314, P=0.022). Increased frequency of the risk allele was seenin younger individuals with CAD where 40% individuals in the age group 30–55 years had the CC genotypeas compared with 29 and 24.5% in the age group 56–65 years and >65 years, respectively (CC versus GG,P=0.045). Higher incidence of the CC genotype was seen in MI patients, but missed significance when comparedwith controls (OR=1.361, 95%CI=0.954–1.942, P=0.084).In conclusion, the rs1333049 variant is significantly associated with CAD risk and also with age of onset inthe Western Indian population. However there are differences in the haplotype structure of this SNP with theneighbouring rs10757278 SNP, these differences emphasize the importance of genotyping all risk variants atthis locus which could underlie the differences in risk susceptibility to CAD across populations.