2017

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2017/№8

Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated With Ischemic Heart Disease in Patients With Type 2 Diabetes

Klimontov V. V., Shevchenko A. V., Tyan N. V., Bulumbaeva D. M., Prokof ’ev V. F., Konenkov V. I.
Scientific Institute of Clinical and Experimental Lymphology, Novosibirsk, Russia

Keywords: ischemic heart disease; diabetes; gene polymorphism; cytokine; matrix metalloproteinase

DOI: 10.18087/cardio.2017.8.10011

Objective. To examine associations between ischemic heart disease (IHD) and polymorphisms in cytokine genes (IL-1B, IL-4, IL-6, IL-10, TNFA, VEGF) and matrix metalloproteinase genes (MMP2, MMP3, MMP9) in patients with type 2 diabetes. Material and methods. We studied 232 Caucasian diabetic subjects (33 men and 199 women aged 50–70 years). In 93 patients IHD was verified by treadmill test and/or coronary angiography (86 subjects with stable angina, 19 with previous myocardial infarction). Thirteen polymorphisms localized in the promoters of IL-1B (rs1143627), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800872, rs1800896), TNFA (rs361525, rs1800629, rs1800630), VEGF (rs699947, rs3025039), MMP2 (rs243865), MMP3 (rs3025058) and MMP9 (rs3918242) were investigated. Results. Prevalence of G-allele and GG-genotype at –308 position of TNFA (rs1800629), as well as C-allele and CC-genotype at position +936 of VEGF (rs3025039) was higher in patients with IHD as compared to patients without IHD (OR=2.0, OR=2.2, OR=2.1, OR=2.4, respectively, all p=0.02). In logistic regression analysis, TNFA –308 A/G and VEGF +936 C/T polymorphisms showed associations with IHD (both p=0.009). These polymorphisms along with age, body mass index, duration of diabetes, low density and high density lipoprotein cholesterol were associated with IHD in multivariate models (p=0.0002 and p=0.00008, respectively). Nine combinations of TNFA –308 GG-genotype and variants of other genes demonstrated associations with IHD (p≤0.002). Conclusion. The polymorphisms in promoter regions of TNFA (rs1800629) and VEGF (rs3025039) are associated with IHD in patients with type 2 diabetes.
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Klimontov V. V., Shevchenko A. V., Tyan N. V., Bulumbaeva D. M., Prokof ’ev V. F., Konenkov V. I. Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated With Ischemic Heart Disease in Patients With Type 2 Diabetes. Kardiologiia. 2017;57(8):5–10.

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