Functional study of -724I/D polymorphism in apolipoprotein M (apoM) gene promoter region and its association with myocardial infarction

Med Sci Monit. 2015 Jan 31:21:371-5. doi: 10.12659/MSM.893077.

Abstract

Background: The aim of this study was to detect the function of -724I/D polymorphism in the apolipoprotein M (apoM) gene promoter region and to determine its relationship with myocardial infarction (MI).

Material/methods: We selected 309 patients with MI and 309 healthy controls for this case-control study. The PCR products of the apoM gene promoter region were directly sequenced to analyze the -724I/D polymorphism. Differences in frequency distributions of genotype and allele were compared between the MI group and the control group. We used gene recombination and site-directed mutagenesis technique to observe the impact of -724 I/D on transcription activity of apoM gene promoter in vitro.

Results: The allele frequency of the -724Del in the MI group was higher than that in the control group (9.5% vs. 3.2%, OR=3.156, 95% CI (1.876~5.309), P<0.001). Compared to the I/I genotype carriers, the apoM levels decreased but the total cholesterol (TC) levels increased significantly in the -724Del allele carriers in plasma. The activity of apoM I/I genotype promoter decreased significantly after the deletion mutation at -724 position in apoM gene.

Conclusions: -724 I/D polymorphism decreases the apoM promoter activity, down-regulates the apoM protein expression level, and increases the risk of MI.

MeSH terms

  • Aged
  • Alleles
  • Apolipoproteins / genetics*
  • Apolipoproteins M
  • Case-Control Studies
  • Cholesterol, HDL / metabolism
  • Coronary Angiography
  • Coronary Artery Disease / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lipocalins / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Myocardial Infarction / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*

Substances

  • APOM protein, human
  • Apolipoproteins
  • Apolipoproteins M
  • Cholesterol, HDL
  • Lipocalins