on October 19, 2007
Published online before print October 19, 2007, doi: 10.1161/ATVBAHA.107.153858
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Submitted on February 27, 2007
Accepted on October 4, 2007
Genetic Variation in ABCA1 Predicts Ischemic Heart Disease in the General Population
Ruth Frikke-Schmidt ;
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, University of Copenhagen, Denmark.
* To whom correspondence should be addressed. E-mail: anne.tybjaerg.hansen{at}rh.regionh.dk.
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.
Key words: atherosclerosis • cardiovascular diseases • genetics • lipids • lipoproteins
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