Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-γ2 gene polymorphism

Aim. To define the pharmacogenetic features of the effect of metformin in coronary heart disease (CHD) patients with metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM), by taking into consideration PPAR-gamma 2 Pro12Ala polymorphism. Subjects and methods. Twenty-four men with CHD and MS and 28 men with CHD and T2DM were examined. The effect of metformin as a short course in combination therapy was evaluated. A population control group consisted of 46 apparently healthy men. The genetic PPRA-gamma 2 Pro12Ala polymorphism was studied. A number of indicators (total cholesterol (TC), high-density lipoprotein cholesterol, total lipids, triglycerides, beta-lipoproteins, glycated hemoglobin, C-peptide) and proinflammatory markers, such as interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were determined in the blood. Results. Analysis of the frequencies of Pro and Ala alleles indicated a decrease in the latter in CHD patients with T2DM. The CHD and MS patients who carried the Pro allele showed a significant metformin-induced reduction in weight, waist circumference, body mass index, and concentrations of TC, C-peptide, and cytokines, such IL-1 beta, IL-6, IL-8, and TNF-alpha. Conclusion. Metformin exhibits a high therapeutic efficacy in patients with CHD in the presence of T2DM or MS who have the Pro/Pro genotype, which is of interest in terms of pharmacogenetics and calls for further investigation.