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

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. (Circ Cardiovasc Genet. 2008;1:85-92.)