The influence of two variants in the adenosine triphosphate-binding cassette transporter 1 gene on plasma lipids and carotid atherosclerosis

Variants in the adenosine triphosphate–binding-cassette transporter 1 (ABCA1) gene are known to affect high-density lipoprotein cholesterol and plasma triglycerides and the development of atherosclerosis. We investigated the influence of the R219K and I883M variants in the ABCA1 gene on plasma lipids and carotid intima media thickness and plaque extent in 688 healthy men (40-60 years old). The R219K variant showed no effect on plasma lipids, but carriers of the K allele displayed a lower intima media thickness (P = .001) and a reduced risk of advanced plaque extent (odds ratio [OR], 0.59; 0.39-0.88; P = .009) compared with noncarriers. However, this risk reduction was observed in nonsmokers only (OR, 0.47; 0.27-0.80; P < .001), but not in smokers (OR, 0.75; 0.41-1.39; P = .2). The I883M variant showed no effect on plasma lipids or carotid atherosclerosis. Risk of advanced plaque extent was reduced in subjects carrying the R219K variant alone (OR, 0.59; 0.38-0.94; P = .025), but not in subjects carrying both variants. Haplotype distribution did not differ between subjects with and without advanced atherosclerosis irrespective of smoking history. We conclude that smoking abrogates the protective effect of the R219K.