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Original Articles

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

Benjamin D. Horne, PhD, MPH; John F. Carlquist, PhD; Joseph B. Muhlestein, MD; Tami L. Bair, BS and Jeffrey L. Anderson, MD

From the Cardiovascular Department (B.D.H., J.F.C., J.B.M., T.L.B., J.L.A.), Intermountain Medical Center, Murray, Utah; Genetic Epidemiology Division (B.D.H.), Department of Biomedical Informatics, University of Utah, and Cardiology Division (J.F.C., J.B.M., J.L.A.), Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

Correspondence to Benjamin D. Horne, PhD, MPH, Cardiovascular Department, Intermountain Medical Center, 5121 S. Cottonwood St., Murray, UT 84157. E-mail benjamin.horne{at}imail.org

Received May 20, 2008; accepted September 3, 2008.

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

Methods and Results— Patients undergoing coronary angiography during 1994 to 2007 (population set 1A: n=1748; set 1B: n=1014) were evaluated for association of a 9p21 tagging single-nucleotide polymorphism (rs2383206, A 224 G) with incident MI and death events among patients with angiographically significant CAD. Another hypothesis evaluated rs2383206 in 2 additional angiographic sets of both CAD and non-CAD patients (set 2A: n=2122; set 2B: n=1466) for prevalent MI versus CAD/no MI (and for MI versus non-CAD and CAD/no MI versus non-CAD). No association of rs2383206 was found with events in set 1A (odds ratio, 0.95 per G allele; P trend=0.48) and set 1B (odds ratio, 0.91 per G allele; P trend=0.28) or with MI versus CAD/no MI in set 2A (odds ratio, 0.96 per G allele; P trend=0.57) and set 2B (odds ratio, 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 because of 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 coronary heart disease pathophysiology.

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

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