3 years ago

Polymorphisms of Intracellular Cholesterol Transporters Genes: Relationship to Blood Lipid Levels, Carotid Intima-Media Thickness, and the Development of Coronary Heart Disease

M. I. Churilin, S. I. Kononov, Yu. V. Luneva, V. A. Kazanov, I. E. Azarova, E. Yu. Klyosova, M. A. Bykanova, G. Paschoalini, A. V. Kharchenko, S. N. Zhabin, O. Yu. Bushueva, S. V. Povetkin, G. S. Mal, A. P. Kovalev, M. A. Solodilova, A. V. Polonikov
The influence of single nucleotide polymorphism (SNP) of genes encoding intracellular cholesterol transporters, such as rs1883025 of ABCA1, rs217406 of NPC1L1, and rs881844 of STARD3, on blood lipid levels, carotid intima-media thickness (CIMT), and the risk of coronary heart disease (CHD) has been studied. SNP genotyping was performed using the MassARRAY 4 system. The effects of polymorphic genes on transformed values of blood lipids and CIMT were evaluated by linear regression analysis separately in men and women and adjusted for age and body mass index. SNP rs881844 of the STARD3 gene was associated with decreased risk of CHD in men (OR = 0.67, 95% CI 0.46–0.96, P = 0.02). In women, SNP rs1883025 of ABCA1 showed an association with decreased risk of CHD (OR = 0.65, 95% CI 0.44–0.95, P = 0.02). In men, SNP rs1883025 of the ABCA1 gene was associated with the levels of low density lipoprotein cholesterol (P = 0.05), whereas SNP rs217406 was associated with triglyceride levels (P = 0.02). Polymorphisms such as rs217406 of NPC1L1 and rs881844 of STARD3 in women and rs1883025 of ABCA1 in men were associated with CIMT. The present study has identified for the first time that rs1883025 of ABCA1 and rs881844 of STARD3 are associated with susceptibility to coronary heart disease and showed clear sex-specific differences in the associations between the genes and the studied phenotypes. Thus, polymorphic variants of genes encoding intracellular cholesterol transporters are potentially involved in the formation of the atherosclerotic process through the mechanisms that seem to be not directly related to the metabolism of cholesterol and cholesterol of low density lipoproteins.

Publisher URL: http://link.springer.com/article/10.1134/S1022795420020040

DOI: 10.1134/S1022795420020040

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