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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:180.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Genetic Variation in ABCA1 Predicts Ischemic Heart Disease in the General Population

Ruth Frikke-Schmidt; Børge G. Nordestgaard; Gorm B. Jensen; Rolf Steffensen; Anne Tybjærg-Hansen

From the Department of Clinical Biochemistry (R.F.-S., A.T.-H.), Rigshospitalet, Copenhagen University Hospital, University of Copenhagen; the Department of Clinical Biochemistry (B.G.N.), Herlev University Hospital, University of Copenhagen; the Copenhagen City Heart Study (B.G.N., G.B.J., A.T.-H.), Bispebjerg University Hospital, University of Copenhagen; and the Department of Medicine B (R.S.), Hillerød Hospital, Hillerød, Denmark.

Correspondence to Anne Tybjærg-Hansen, MD, DMSc, Chief Physician and Associate Professor, Department of Clinical Biochemistry KB 3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail anne.tybjaerg.hansen{at}rh.regionh.dk

Abstract

Objective— We tested the hypothesis that 6 nonsynonymous single nucleotide polymorphisms (SNPs) in ATP-Binding-Cassette transporter A1 (ABCA1) affect risk of ischemic heart disease (IHD) in the general population.

Methods and Results— We genotyped 9259 individuals from the Danish general population followed for 25 years. Two SNPs (V771M and V825I) were previously associated with increases in HDL-C, 1 (R1587K) with decreased HDL-C, whereas 3 (R219K, I883M and E1172D) did not affect HDL-C levels. Despite this, 5 out of 6 SNPs (V771M, V825I, I883M, E1172D, R1587K) predicted increased risk of IHD. Similar results were obtained in a verification sample with 932 IHD cases versus 7999 controls. A stepwise regression approach identified V771M, I883M, and E1172D as the most important predictors of IHD and additive effects on IHD risk were present for V771M/I883M and I883M/E1172D pairs.

Conclusions— We show that 3 of 6 nonsynonymous SNPs in ABCA1 predict risk of IHD in the general population.

We tested whether nonsynonymous SNPs in ABCA1 affect risk of IHD in the general population. We show that 3 of 6 nonsynonymous SNPs in ABCA1 predict risk of IHD in the general population.

Key Words: atherosclerosis • cardiovascular diseases • genetics • lipids • lipoproteins