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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1613.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Gene Variants of VAMP8 and HNRPUL1 Are Associated With Early-Onset Myocardial Infarction

Dov Shiffman; Charles M. Rowland; Judy Z. Louie; May M. Luke; Lance A. Bare; Joel I. Bolonick; Bradford A. Young; Joseph J. Catanese; Charles F. Stiggins; Clive R. Pullinger; Eric J. Topol; Mary J. Malloy; John P. Kane; Stephen G. Ellis; James J. Devlin

From Celera Inc. (D.S., C.M.R., J.Z.L., M.M.L., L.A.B., J.I.B., B.A.Y., J.J.C., J.J.D.), Alameda, Calif; Brigham Young University (C.F.S.), University Station, Provo, Utah; Cardiovascular Research Institute (C.R.P., M.J.M., J.P.K.), University of California San Francisco; Case Western Reserve University (E.J.T.), Department of Genetics, Cleveland, Ohio; and the Cleveland Clinic Foundation (S.G.E.), Department of Cardiovascular Medicine, Ohio.

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

Objectives— Identify gene variants associated with early-onset myocardial infarction (MI).

Methods and Results— We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (P<0.05) in study 1, we tested these SNPs in study 2 (434 cases, 504 controls). We found that 8 of the 666 SNPs were associated with early-onset MI in study 2 (P<0.05) and had the same risk alleles as in study 1. These 8 SNPs were then tested for association with early-onset MI in study 3 (187 cases, 434 controls). We found that a VAMP8 variant (P=0.025; odds ratio [OR], 1.75; CI, 1.17 to 2.62) and an HNRPUL1 variant (P=0.0043; OR, 1.92; CI, 1.28 to 2.86) were associated with early-onset MI (nominal P<0.05; false discovery rate <10%) and had the same risk alleles in all 3 studies.

Conclusions— Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.

Genetic associations with early-onset myocardial infarction were identified by testing successively fewer SNPs in 3 consecutive case-control studies. Thus, 11 647 SNPs were tested in the first study, 666 in the second study, and only 8 SNPs were tested in the third study.

Key Words: myocardial infarction • genetics • single nucleotide polymorphism • risk factors

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