Association Between the Chromosome 9p21 Locus and Angiographic Coronary Artery Disease Burden A Collaborative Meta-Analysis

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:61

Article

Chan, Kenneth¹  Patel, Riyaz S.^1,2,3  Newcombe, Paul⁴  Nelson, Christopher P.⁵  Qasim, Atif⁶  Epstein, Stephen E.⁷  Burnett, Susan⁷  Vaccarino, Viola L.⁸  Zafari, A. Maziar⁸  Shah, Svati H.⁹  Anderson, Jeffrey L.¹⁰  Carlquist, John F.¹⁰  Hartiala, Jaana⁹  Allayee, Hooman⁹  Hinohara, Kunihiko¹¹  Lee, Bok-Soo¹²  Erl, Anna¹³  Ellis, Katrina L.¹⁴  Goel, Anuj¹⁵  Schaefer, Arne S.¹⁶  El Mokhtari, Nour Eddine^16,17  Goldstein, Benjamin A.¹⁸  Hlatky, Mark A.¹⁸  Go, Alan S.¹⁹  Shen, Gong-Qing²⁰  Gong, Yan¹⁴  Pepine, Carl¹⁴  Laxton, Ross C.¹  Whittaker, John C.²²  Tang, W. H. Wilson²²  Johnson, Julie A.²¹  Wang, Qing K.²⁰  Assimes, Themistocles L.¹⁸  Noethlings, Ute^23,24,25  Farrall, Martin^15,26  Watkins, Hugh^15,26  Richards, A. Mark¹⁴  Cameron, Vicky A.¹⁴  Muendlein, Axel²⁷  Drexel, Heinz²⁷  Koch, Werner¹³  Park, Jeong Euy¹²  Kimura, Akinori¹¹  Shen, Wei-feng²⁸  Simpson, Iain A.²⁹  Hazen, Stanley L.^23,24,25  Horne, Benjamin D.¹⁰  Hauser, Elizabeth R.⁹  Quyyumi, Arshed A.³  Reilly, Muredach P.⁶  Samani, Nilesh J.⁵  Ye, Shu¹ 

[1] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England

[2] Cardiff Univ, Dept Med, Cardiff CF10 3AX, S Glam, Wales

[3] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA

[4] MRC Biostat Unit, Cambridge, England

[5] Glenfield Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester, Leics, England

[6] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA

[7] Washington Hosp Ctr, MedStar Hlth Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA

[8] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA

[9] Duke Univ, Dept Med, Ctr Human Genet, Durham, NC USA

[10] Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA

[11] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pathogenesis, Tokyo, Japan

[12] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Cardiol, Seoul, South Korea

[13] German Heart Ctr, Munich, Germany

[14] Univ Otago, Dept Med, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand

[15] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[16] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[17] Kreiskrankenhaus Rendsburg, Innere Med Klin, Rendsburg, Germany

[18] Stanford Univ, Dept Med, Stanford, CA USA

[19] Kaiser Permanente, Div Res, Oakland, CA USA

[20] Cleveland Clin, Dept Mol Cardiol, Ctr Cardiovasc Genet, Dept Cardiovasc Med, Cleveland, OH 44106 USA

[21] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA

[22] London Sch Hyg & Trop Med, London WC1, England

[23] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44106 USA

[24] Univ Kiel, Epidemiol Sect, Inst Expt Med, Kiel, Germany

[25] Univ Hosp Schleswig Holstein, PopGen Biobank, Kiel, Germany

[26] Univ Oxford, Dept Cardiovasc Med, Oxford, England

[27] VIVIT, Feldkirch, Austria

[28] Shanghai Jiao Tong Univ, Dept Cardiol, Rui Jin Hosp, Sch Med, Shanghai 200030, Peoples R China

[29] Southampton Univ Hosp, Wessex Reg Cardiac Unit, Southampton, Hants, England

关键词: 9p21;    angiography;    coronary artery disease;    meta-analysis;    myocardial infarction;    single nucleotide polymorphism;   

DOI  :  10.1016/j.jacc.2012.10.051

来源: Elsevier

【 摘 要 】

Objectives This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD. Background Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. Methods We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects. Results We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele. Conclusions The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype. (J Am Coll Cardiol 2013; 61: 957-70) (C) 2013 by the American College of Cardiology Foundation

【 授权许可】

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