title: ATP-binding cassette transporter A1 gene I823M polymorphism affects plasma high-density lipoprotein cholesterol level and modifies the effect of low high-density lipoprotein cholesterol on the risk of coronary artery disease.
abstract: BACKGROUND
  The I823M polymorphism of the ATP-binding cassette transporter A1 (ABCA1) gene has been reported to affect plasma high-density lipoprotein cholesterol (HDL-C) level. Information about its relationship to coronary artery disease (CAD) is limited.
  
  
  RESULTS
  We included 205 patients with angiographically documented CAD and 201 controls from the general population. We found that I823M 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 < or = 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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.forename: Juey-Jen
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Fu-Tien
authors.initials: FT
authors.lastname: Chiang
authors.forename: Chuen-Den
authors.initials: CD
authors.lastname: Tseng
authors.forename: Jiunn-Lee
authors.initials: JL
authors.lastname: Lin
authors.forename: Yung-Zu
authors.initials: YZ
authors.lastname: Tseng
authors.forename: Ling-Ping
authors.initials: LP
authors.lastname: Lai
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D005819:Genetic Markers