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

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Abstract

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.

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Authors and Affiliations

  1. Kursk State Medical University, 305041, Kursk, Russia

    M. I. Churilin, S. I. Kononov, Yu. V. Luneva, V. A. Kazanov, I. E. Azarova, G. Paschoalini, A. V. Kharchenko, S. N. Zhabin, O. Yu. Bushueva, S. V. Povetkin, G. S. Mal, M. A. Solodilova & A. V. Polonikov

  2. Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041, Kursk, Russia

    I. E. Azarova, E. Yu. Klyosova, M. A. Bykanova, O. Yu. Bushueva & A. V. Polonikov

  3. Kursk Regional Clinical Blood Transfusion Station, 305035, Kursk, Russia

    A. P. Kovalev

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Churilin, M.I., Kononov, S.I., Luneva, Y.V. et al. Polymorphisms of Intracellular Cholesterol Transporters Genes: Relationship to Blood Lipid Levels, Carotid Intima-Media Thickness, and the Development of Coronary Heart Disease. Russ J Genet 56, 234–241 (2020). https://doi.org/10.1134/S1022795420020040

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