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

• Type of Material: Article
• Authors: Kenneth Chan, Queen Mary University; Riyaz S. Patel, Queen Mary University; Paul Newcombe, MRC Biostatistics Unit; Christopher P. Nelson, Glenfield Hospital; Atif Qasim, University of Pennsylvania; Stephen E. Epstein, Washington Hospital Center; Susan Burnett, Washington Hospital Center; Viola Vaccarino, Emory University; A. Maziar Zafari, Emory University; Svati H. Shah, Duke University; Jeffrey L. Anderson, Intermountain Medical Center; John F. Carlquist, Intermountain Medical Center; Jaana Hartiala, Duke University; Hooman Allayee, Duke University; Kunihiko Hinohara, Tokyo Medical and Dental University; Bok-Soo Lee, Sungkyunkwan University; Anna Erl, German Heart Center; Katrina L. Ellis, University of Otago; Anuj Goel, University of Oxford; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2013-03-05
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American College of Cardiology Foundation.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacc.2012.10.051
• Title of Journal or Parent Work: Journal of the American College of Cardiology
• ISSN: 0735-1097
• Volume: 61
• Issue: 9
• Start Page: 957
• End Page: 970
• Grant/Funding Information: Complete funding list available in full text.
• Keywords: Cardiovascular System & Cardiology; angiography; PROGRESSION; RISK; REPLICATION; Life Sciences & Biomedicine; coronary artery disease; meta-analysis; 9p21; COMMON VARIANT; Cardiac & Cardiovascular Systems; ATHEROSCLEROSIS; myocardial infarction; single nucleotide polymorphism; Science & Technology; GENETIC-VARIATION; SUSCEPTIBILITY LOCUS; PREDICTS SEVERITY; GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION
• Research Categories: Health Sciences, Epidemiology; Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

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.