Four SNPs on Chromosome 9p21 in a South Korean Population Implicate a Genetic Locus That Confers High Cross-Race Risk for Development of Coronary Artery Disease

Abstract

Objective— Recent genome-wide association studies have identified 4 SNPs on chromosome 9p21 associated with CAD (rs10757274 and rs2383206) and myocardial infarction (MI: rs2383207 and rs10757278) in White populations in Northern Europe and North America. We aimed to determine whether this locus confers significant susceptibility to CAD in a South Korean population, and thus cross-race susceptibility to CAD. Methods and Results— We performed a case-control association study with 611 unrelated CAD patients and 294 normal controls from South Korea. Allelic associations of SNPs and SNP haplotypes with CAD were evaluated. Multivariate logistic regression analysis was used to adjust effects of clinical covariates. We found that 4 SNPs on chromosome 9p21 were associated with susceptibility to CAD in a South Korean population. The association remained significant after adjusting for significant clinical covariates ( P =0.001 to 0.024). We identified one risk haplotype (GGGG; P =0.017) and one protective haplotype (AAAA; P =0.007) for development of CAD. Further analysis suggested that the SNPs probably confer susceptibility to CAD in a dominance model (covariates-adjusted P =0.001 to 0.024; OR=2.37 to 1.54). This represents the first study that expands association of these 9p21 SNPs with CAD beyond White populations. Conclusion— Chromosome 9p21 is an important susceptibility locus that confers high cross-race risk for development of CAD.

Genome-wide association study of coronary artery disease in the Japanese

“…6,9 In addition, the present genome-wide exploration identified significant association near CDKN2A/B in East Asians, as previously reported in European-descent populations. 1,2,5,7,8 Of the three loci, which we claim to be associated with CAD in the Japanese GWA study (Table 2), the disease association at two loci -12q24 and 9p21 -have been reported in several Asian populations 10,11,26 and could be regarded confirmatory. Nevertheless, two novel findings are noted in our study: (1) the other locus within an HLA gene, HLA-DQB1, which is considered to explain the previous descriptions of CAD (in particular, MI) association signals on 6p21 in the Japanese 21 and (2) a pronounced association with MI, as compared with CAD, for the variants on 12q24.…”

Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people

“…This analysis showed that these factors are highly relevant to CAD with an adjusted OR ranging from 3.00-6.06 (P < 0.05), indicating that they are risk factors for CAD in the Chinese Han population. Shen et al (2008a), studying populations from South Korea, observed that the rs10757274 and rs10757278 alleles were highly correlated with CAD with ORs of 1.29 (95%CI = 1.06-1.58) and 1.29 (95%CI =1.06-1.57), respectively. rs10757274 and rs10757278 are located near the CDKN2A and CDKN2B genes, which encode proteins with important roles in the regulation of many cellular processes, including cell proliferation, maturation, senescence, and programmed cell death.…”

New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing

“…This SNP was furthermore identified as a risk locus for ischaemic stroke (odds ratio = 1.59 (1.20-2.11), P = 0.004) 24,25 and sudden cardiac death (meta-analysis of six independent cohort studies: odds ratio = 1.21 (1.04-1.40), P = 0.01) 26 . We also identified a homozygous minor allele of rs2383206 (GG), which is another major CHD and ischaemic risk SNP with a hazard ratio of 1.26 (1.07-1.48) 23 and 1.30 (1.06-1.58) 27 , respectively. In combination with rs10757274 the risk for developing CHD almost doubles 28 .…”