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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:173.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Association of Gene Variants With Incident Myocardial Infarction in the Cardiovascular Health Study

Dov Shiffman; Ellen S. O’Meara; Lance A. Bare; Charles M. Rowland; Judy Z. Louie; Andre R. Arellano; Thomas Lumley; Kenneth Rice; Olga Iakoubova; May M. Luke; Bradford A. Young; Mary J. Malloy; John P. Kane; Stephen G. Ellis; Russell P. Tracy; James J. Devlin; Bruce M. Psaty

From Celera (D.S., L.A.B., C.M.R., J.Z.L., A.R.A., O.I., M.M.L., B.A.Y., J.J.D.), Alameda, Calif; the Department of Biostatistics (E.S.O., T.L., K.R.), School of Public Health and Community Medicine, University of Washington, Seattle; the Cardiovascular Health Research Unit (T.L., B.M.P.), University of Washington, Seattle; the Cardiovascular Research Institute (M.J.M., J.P.K.), University of California San Francisco; The Cleveland Clinic Foundation (S.G.E.), Department of Cardiovascular Medicine, Cleveland, Ohio; the Departments of Pathology and Biochemistry (R.P.T.), College of Medicine, University of Vermont, Burlington; the Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Washington, Seattle; and the Center for Health Studies (B.M.P.), Group Health, Seattle, Wash.

Correspondence to Dov Shiffman, Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502. E-mail dov.shiffman{at}celera.com

Abstract

Objective— We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.

Methods and Results— Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided P<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HR=1.29; 90%CI 1.1 to 1.52), VAMP8 (HR=1.2; 90%CI 1.02 to 1.41), TAS2R50 (HR=1.13; 90%CI 1 to 1.27), and LPA (HR=1.62; 90%CI 1.09 to 2.42).

Conclusions— Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.

We identified 4 SNPs (in KIF6, VAMP8, LPA, and TAS2R50) that are associated with increased risk of incident MI in CHS, a prospective study of adults aged 65 years or older.

Key Words: coronary disease • myocardial infarction • genetics • polymorphisms

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