Klimenko N. Influence of the PPAR- gene polymorphism on the clinical manifestations and effectiveness of sartans in patients with hypertension, obesity and type 2 diabetes.

The dissertation is dedicated to improving the effectiveness of treatment of hypertension in patients with obesity and type 2 diabetes based on the investigation of adiponectin and leptin levels, in dependence on the PPAR-? gene polymorphism, and estimation of the clinical effects of complex therapy with telmisartan or candesartan. Among the 104 examined patients with hypertension, obesity with and without type 2 diabetes. The genotype Ala12Ala was found only once - 1 (0.09%), Pro12 Ala heterozygotes were 18 (17.3%) and homozygotes Pro12Pro - 85 (82.7%). It is established that the presence of single nucleotide PPAR-? polymorphisms leads to changes in carbohydrate and lipid metabolism, concentrations of leptin, adiponectin and C-reactive protein. Hypertension in combination with obesity and type 2 diabetes is characterized by an adipocytokines imbalance. The relationship between adiponectin levels and the number of accompanying cardiovascular risk factors was demonstrated. It was proven that the 24-week treatment with telmisartan is associated with the significant increase in the adiponectin concentration, the increased sensitivity of peripheral tissues to insulin, which leads to a decline in glycosylated hemoglobin levels and HOMA index and favours lowering of triglyceride levels. In this case, these effects were more pronounced in patients with a partial polymorphism Pro12Ala, than in homozygotes Pro12Pro (respectively r = 0.81, p <0.05 and r = 0.70, p <0.05). It was found that patients with obesity, hypertension and type 2 diabetes metabolic efficiency of sartans varies in relation to the PPAR-? genotype and was better in patients with genotype X / Ala compared with Pro12Pro.