Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis.

MedStar author(s):
Citation: Journal of the American College of Cardiology. 61(9):957-70, 2013 Mar 5.PMID: 23352782Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *Chromosomes, Human, Pair 9/ge [Genetics] | *Coronary Artery Disease/ge [Genetics] | Coronary Angiography | Coronary Artery Disease/ra [Radiography] | Genetic Loci | Humans | Myocardial Infarction/ge [Genetics] | Polymorphism, Single NucleotideLocal holdings: Available online from MWHC library: 1995 - present, Available in print through MWHC library:1999-2007ISSN:
  • 0735-1097
Name of journal: Journal of the American College of CardiologyAbstract: 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.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. Copyright 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.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.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.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.All authors: Allayee H, Anderson JL, Assimes TL, Burnett S, Cameron VA, Carlquist JF, Chan K, Drexel H, El Mokhtari NE, Ellis KL, Epstein SE, Erl A, Farrall M, Go AS, Goel A, Goldstein BA, Gong Y, Hartiala J, Hauser ER, Hazen SL, Hinohara K, Hlatky MA, Horne BD, Johnson JA, Kimura A, Koch W, Laxton RC, Lee BS, Muendlein A, Nelson CP, Newcombe P, Nothlings U, Park JE, Patel RS, Pepine C, Qasim A, Quyyumi AA, Reilly MP, Richards AM, Samani NJ, Schaefer AS, Shah SH, Shen GQ, Shen WF, Simpson IA, Tang WH, Vaccarino VL, Wang QK, Watkins H, Whittaker JC, Ye S, Zafari AMDigital Object Identifier: Date added to catalog: 2014-04-22
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 23352782

Available online from MWHC library: 1995 - present, Available in print through MWHC library:1999-2007

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.

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. Copyright 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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