on November 29, 2007
Published online before print November 29, 2007, doi: 10.1161/ATVBAHA.107.157248
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Submitted on October 2, 2007
Accepted on November 19, 2007
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
Gong-Qing Shen ;
From the Department of Molecular Cardiology, Lerner Research Institute; Center for Cardiovascular Genetics; Department of Cardiovascular Medicine; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (G.-Q.S., L.L., S.R., K.G.A., Q.K.W.), Cleveland Clinic, Cleveland, Ohio; and the Samsung Medical Center (J.M.B., B.-S.L., J.E.P.), Sungkyunkwan University, Seoul, South Korea.
* To whom correspondence should be addressed. E-mail: wangq2{at}ccf.org.
Objective—Recent genome-wide association studies have identified 4 SNPs on chromosome 9p21 associated with CAD (rs1075727 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.
Key words: coronary artery disease • myocardial infarction • single nucleotide polymorphism • association study • Asian population