Lavrenko A. Pharmacogenetic study of the use of metformin in the treatment of patient with type 2 diabetes mellitus in combination with coronary heart disease.

The thesis is devoted to improving the treatment of patients with diabetes type 2 in combination with coronary heart disease by pharmacogenetic approaches to the use of metformin based on gene polymorphism PPAR-?2. Frequency analysis in persons carrying allele Pro, and separatly, persons carrying allele Ala, among the inhabitants of Poltava region confirmed that patients with diabetes type 2 in combination with the suspicion of coronary artery disease a prevalence of genotype frequency Pro / Pro has observed, which directly burdens clinic syntropy, due to a genetic predisposition to the development of atherogenic dyslipidemia, insulin resistance, increased activity of pro-inflammatory cytokines, due to the increased expression of NF- kB as an important signaling pathway regulation of metabolic processes. Studied pharmacogenetic dependence of metformin action on the background of traditional therapy in patients who are carriers of allele Pro, significantly positive effects on anthropometric parameters, lipid metabolism, contributing to the reduction of total cholesterol, atherogenic index. Comparative analysis of the results obtained after treatment showed that a significant anti-inflammatory effect of metformin was observed in patients with genotypes Pro / Pro polymorphism of gene Pro12Ala and gene PPAR?2. Firstly, it has been shown that matformin prescribed in patients with diabetes type 2 in combination with coronary heart disease results of increase in number of cells expressing NF- kB , while there is not only an increase in the relative number of cells , but also decrease the dispersion of results. Analysis of clinical manifestations in patients with diabetes type 2 in combination with coronary artery disease and genotype Pro / Pro, receiving metformin due to the standard complex therapy, revealed decreased severity of angina, improved quality of life after 3 months of observation. The obtained results of clinical manifestations indicate an absence of direct effects of metformin on the disease in patients with genotypes Pro / Ala and Ala / Ala.