Polymorphisms in genes of cytokines and matrix metalloproteinases associated with ischemic heart disease in patients with type 2 diabetes

Abstract

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 (rsll43627), IL-4 (rs2243250), IL-6 (rsl800795), IL-10 (rsl800872, rsl800896), TNFA (rs361525, rsl800629, rsl800630), 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 (rsl800629), 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.