This Article Full Text Full Text (PDF) All Versions of this Article: 28/2/360    most recent ATVBAHA.107.157248v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shen, G.-Q. Articles by Wang, Q. K. Search for Related Content PubMed PubMed Citation Articles by Shen, G.-Q. Articles by Wang, Q. K.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:360.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

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; Lin Li; Shaoqi Rao; Kalil G. Abdullah; Ji Min Ban; Bok-Soo Lee; Jeong Euy Park; Qing K. Wang

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. Key Laboratory of Molecular Biophysics of Ministry of Education, Huo Zhong University of Science and Technology, Wuhan, China (Q.K.W.).

Correspondence to Qing K. Wang, PhD, MBA, Center for Cardiovascular Genetics NE40, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195. E-mail wangq2{at}ccf.org or Jeong Euy Park, MD, Sungkyun Kwan University, Seoul, South Korea. E-mail jpark@smc.samsung.co.kr

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.

A case-control association study in a South Korean population finds that 4 SNPs previously implicated to be associated with CAD in European populations also confer risk in an Asian population. We conclude that chromosome 9p21 is a susceptibility locus associated with increased cross-race risk of development of CAD.

Key Words: coronary artery disease • myocardial infarction • single nucleotide polymorphism • association study • Asian population

This article has been cited by other articles:

				C. Fan, P. Ouyang, A. A. Timur, P. He, S.-A. You, Y. Hu, T. Ke, D. J. Driscoll, Q. Chen, and Q. K. Wang Novel Roles of GATA1 in Regulation of Angiogenic Factor AGGF1 and Endothelial Cell Function J. Biol. Chem., August 28, 2009; 284(35): 23331 - 23343. [Abstract] [Full Text] [PDF]

				H. Ding, Y. Xu, X. Wang, Q. Wang, L. Zhang, Y. Tu, J. Yan, W. Wang, R. Hui, C.-Y. Wang, et al. 9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population Circ Cardiovasc Genet, August 1, 2009; 2(4): 338 - 346. [Abstract] [Full Text] [PDF]

				K. Yamagishi, A. R. Folsom, W. D. Rosamond, E. Boerwinkle, and for the ARIC Investigators A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study Eur. Heart J., May 2, 2009; 30(10): 1222 - 1228. [Abstract] [Full Text] [PDF]

				N. J. Samani and H. Schunkert Chromosome 9p21 and Cardiovascular Disease: The Story Unfolds Circ Cardiovasc Genet, December 1, 2008; 1(2): 81 - 84. [Full Text] [PDF]

				B. D. Horne, J. F. Carlquist, J. B. Muhlestein, T. L. Bair, and J. L. Anderson Association of Variation in the Chromosome 9p21 Locus With Myocardial Infarction Versus Chronic Coronary Artery Disease Circ Cardiovasc Genet, December 1, 2008; 1(2): 85 - 92. [Abstract] [Full Text] [PDF]

				L. Zhou, X. Zhang, M. He, L. Cheng, Y. Chen, F. B. Hu, and T. Wu Associations Between Single Nucleotide Polymorphisms on Chromosome 9p21 and Risk of Coronary Heart Disease in Chinese Han Population Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 2085 - 2089. [Abstract] [Full Text] [PDF]