Effect of 9p21 genetic variation on coronary heart disease is not modified by other risk markers. The Atherosclerosis Risk in Communities (ARIC) Study

• Published in: Atherosclerosis 2012-10, Vol.224 (2), p.435-439
• Main Authors: Folsom, Aaron R, Nambi, Vijay, Pankow, James S, Tang, Weihong, Farbakhsh, Kian, Yamagishi, Kazumasa, Boerwinkle, Eric
• Format: Article
• Language: English
• Subjects: 9p21 SNP; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Chromosomes, Human, Pair 9; Coronary Artery Disease - blood; Coronary Artery Disease - ethnology; Coronary Artery Disease - genetics; Coronary disease; Coronary heart disease; Female; Gene Frequency; Gene-Environment Interaction; Genetic Predisposition to Disease; genetic variation; genotype; Heart; Humans; Incidence; Male; Medical sciences; Middle Aged; natriuretic peptides; Phenotype; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Prospective study; regression analysis; risk; Risk Assessment; Risk Factors; single nucleotide polymorphism; troponin T; United States - epidemiology; White People - genetics
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2012.08.007

Abstract Objective To determine whether the 9p21 SNP association with coronary heart disease is modified by other classical or novel risk markers. Methods The 9p21 SNP (rs10757274) and multiple risk markers were measured in the Atherosclerosis Risk in Communities Study, and incident coronary disease events were ascertained. Effect modification (interaction) of the 9p21 SNP with risk markers was tested in Cox proportional hazard regression models. Results The incidence rates of coronary heart disease per 1000 person-years were 14.4, 17.0, and 18.7 for AA, AG, and GG genotypes, yielding hazard ratios of 1.0, 1.20 (95% CI = 1.07–1.36), and 1.34 (95% CI = 1.16–1.53). There was no meaningful evidence of an interaction (all p -interaction > 0.04) between 9p21 SNP and any of 14 other risk markers for coronary heart disease. These included novel markers not previously explored for 9p21 interaction (e.g., cardiac troponin T and N-terminal pro-brain natriuretic peptide). Conclusion Our study extends evidence that the 9p21 SNP association with coronary heart disease is not modified by classical or novel risk markers. Our findings therefore rule out additional plausible pathways by which 9p21 might have increased coronary heart disease risk.