Association between 9p21.3 genomic markers and coronary artery disease in East Asians: a meta-analysis involving 9,813 cases and 10,710 controls

Abstract

Recently, genome-wide association studies on coronary artery disease (CAD) identified a series of associated single-nucleotide polymorphisms (SNPs) in an intergenic region of chromosome 9p21.3, near the CDKN2A and CDKN2B genes. We investigated the association of this locus with CAD in 12 case-control studies of East Asians and undertook a meta-analysis for effect size, heterogeneity, publication bias, and strength of evidence. English and Chinese language articles were tested for 9p21.3 SNPs with coronary heart/artery disease or myocardial infarction as primary outcomes. Included articles also provided race, numbers of participants, and data to compute an odds ratio (OR). Articles were excluded if reporting other outcomes (e.g., stroke). Thirty-five articles were initially identified and 12 were included. Independent extraction was performed by two reviewers and consensus was reached. SNP rs1333049, rs2383206 and rs10757278 representing the 9p21.3 locus, were genotyped in 12 case-control studies involving a total of 9,813 patients and 10,710 controls. For rs1333049 (8 data sets), using a fixed-effects model, the summary OR was 1.29 (95 % CI, 1.23-1.36, P = 0.001). For rs2383206 (6 data sets), using a fixed-effects model, the summary OR was 1.24 (95 % CI, 1.18-1.31, P = 0.001). For rs10757278 (6 data sets), using a random-effects model, the summary OR was 1.34 (95 % CI, 1.21-1.50, P = 0.001). In addition, we defined the haploblock structure of SNPs within the region of 9p21.3 in China population in one study. This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD in East Asians.