Background: TheI823M polymorphism of the ATP-binding cassette transporter A1 (ABCA1) gene has been reported to affect plasmahigh-density lipoprotein cholesterol (HDL-C) level. Information about its relationship to coronary artery disease (CAD) is limited. Methods and Results: We included 205 patients with angiographically documented CAD and 201 controls from the general population. We found thatI823M polymorphism was a significant source of variation of HDL-C (p = 0.024 after adjustment for age, sex, body mass index, smoking and alcohol drinking). Subjects with M823/M823 homozygotes (n = 103) had a higher HDL-C than those with I823/I823 or I823/M823 genotype (n = 98) (50.5 ± 9.7 vs. 47.6 ± 10.1 mg/dl, p = 0.039). I823M polymorphism was not a predictor of CAD in multivariate analysis (adjusted odds ratio = 1.5 [0.9-2.5], p = 0.145). However, it interacted with low HDL-C level to increase the risk of CAD. The odds ratio of CAD with M823 homozygosity was 5.3 (2.0-20.0) in patients with HDL-C ≤35 mg/dl, but was only 1.0 (0.5-2.0) in those with HDL >40 mg/dl (p = 0.039 for interaction). Conclusions: M823 variant of the ABCA1 gene was associated with a higher HDL-C. Furthermore, I823M polymorphism interacted with low-HDL-C on the risk of CAD. It served as a marker to identify high-risk patients for CAD in subjects with low-HDL-C.
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