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31 January 2015 : Clinical Research

Functional Study of -724I/D Polymorphism in Apolipoprotein M (apoM) Gene Promoter Region and its Association with Myocardial Infarction

Hua GuoABCEF, Xian-Xian ZhaoABCEG, Xiao-Juan ZhangABCE, Wei ChenCEF, Jie ZhangACEF

DOI: 10.12659/MSM.893077

Med Sci Monit 2015; 21:371-375

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 AND 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.

Keywords: Apolipoproteins - genetics, Alleles, Case-Control Studies, Cholesterol, HDL - metabolism, Coronary Angiography, Coronary Artery Disease - genetics, Genetic Predisposition to Disease, Genotype, Lipocalins - genetics, Mutation, Myocardial Infarction - genetics, Polymorphism, Genetic, Promoter Regions, Genetic

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750