Published Online
on October 15, 2008

A more recent version of this article appeared on December 1, 2008

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Original Article

Association of Variation in the Chromosome 9p21 Locus with Myocardial Infarction versus Chronic Coronary Artery Disease

Benjamin D. Horne^1,3; John F. Carlquist¹; Joseph B. Muhlestein¹; Tami L. Bair² and Jeffrey L. Anderson¹

¹ Intermountain Medical Center, University of Utah;
² Intermountain Medical Center

³ E-mail: benjamin.horne{at}imail.org

Background—A chromosome 9p21 locus is associated with coronary heart disease (CHD) in at least 25 independent populations, but multiple clinically-distinct phenotypes have been evaluated. Utilizing angiographic coronary artery disease (CAD) phenotyping, this study evaluated whether 9p21 single nucleotide polymorphisms (SNPs) predict ischemic events (e.g., myocardial infarction [MI]) among CAD patients.

Methods and Results—Patients undergoing coronary angiography during 1994-2007 (population set 1A: N=1,748; set 1B: N=1,014) were evaluated for association of a 9p21 tagging SNP (rs2383206, AG) with incident MI and death events among patients with angiographically-significant CAD. Another hypothesis evaluated rs2383206 in two additional angiographic sets of both CAD and non-CAD patients (set 2A: N=2,122; set 2B: N=1,466) for prevalent MI vs. CAD/no MI (and for MI vs. non-CAD and CAD/no MI vs. non-CAD). No association of rs2383206 was found with events in set 1A (OR=0.95 per G allele, p-trend=0.48) and set 1B (OR=0.91 per G allele, p-trend=0.28), or with MI vs. CAD/no MI in set 2A (OR=0.96 per G allele, p-trend=0.57) and set 2B (OR=0.89 per G allele, p-trend=0.21). In contrast, rs2383206 was associated with CAD/no MI compared with non-CAD (set 2A: p-trend=0.0001; set 2B: p-trend=0.0008).

Conclusions—The chromosome 9p21 locus was not associated with incident events or prevalent MI, although it did predict CAD diagnosis. This contradicts reports of a 9p21 association with MI, likely due to differences in phenotype assignment. This suggests that high-quality phenotyping for CAD and MI is required to dissect the specific contributions of genetic variation to each stage of CHD pathophysiology.

Key Words: atherosclerosis • coronary disease • epidemiology • genetics • myocardial infarction

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Chromosome 9p21 and Cardiovascular Disease: The Story Unfolds

Nilesh J. Samani and Heribert Schunkert
Circ Cardiovasc Genet 2008 1: 81-84. [Extract] [Full Text] [PDF]

Association of Variation in the Chromosome 9p21 Locus With Myocardial Infarction Versus Chronic Coronary Artery Disease

Benjamin D. Horne, John F. Carlquist, Joseph B. Muhlestein, Tami L. Bair, and Jeffrey L. Anderson
Circ Cardiovasc Genet 2008 1: 85-92. [Abstract] [Full Text] [PDF]

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