A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Atherosclerosis. 2011 Dec;219(2):648-54. doi: 10.1016/j.atherosclerosis.2011.05.043. Epub 2011 Jun 17.

Abstract

Objective: In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population.

Methods: 1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3'-untranslated region (UTR).

Results: The human ABCG1 -367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 -768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay.

Conclusions: The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.

MeSH terms

  • 3' Untranslated Regions
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Aged
  • Animals
  • Asian People / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • China / epidemiology
  • Coronary Angiography
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / prevention & control
  • Female
  • Gene Frequency
  • Genes, Reporter
  • Genetic Predisposition to Disease
  • HEK293 Cells
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lipids / blood
  • Logistic Models
  • Macrophages / metabolism
  • Male
  • Mice
  • Middle Aged
  • Myocardial Infarction / genetics
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Transfection

Substances

  • 3' Untranslated Regions
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Lipids