P332L162V PPAR-alpha gene polymorphism, A603G tissue factor gene polymorphism and markers of endothelial dysfunction in coronary heart disease patients in Russian population

Purpose. The goal of this study is to determine the effect of structural polymorphism L162V of peroxisome proliferator-activated receptors type α (PPAR-α)gene and structural polymorphism of A603G of TF gene on the molecular markers of endothelial dysfunction in patients with coronary heart disease. Methods. The L162V PPAR-α and A603G TF gene genotypes were determined in a sample of 212 Russian men with CHD and 55 healthy men by a polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based method. Vascular cell adhesion molecule-1 (VCAM-1), IL-8, IFN-γ, IL-6 plasma levels were studied by ELISA (Bender Medsystems). ANOVa analysis, exact Fisher test and Odds-Ratio calculation were performed. Results. The frequency of L162V genotype of PPAR-α gene in coronary heart disease patients was higher than in the group of healthy people (30 from 212 and 2 from 55, p=0.016). The frequency of TF G603G genotype in CHD patients was higher than in the group of healthy people (72 from 212 and 11 from 55, p=0,017). VCAM-1 level of blood plasma in CHD patients was higher than in healthy individuals: 991.6+ 42.3 ng/ml and 657.1+47.4 ng/ml respectively, p 29.9kg/m^2­ the level of VCAM-1 accounted 1080+66.5 ng/ml that is significantly higher than in patients with BMI <=29.9kg/m^2 (885+48 ng/ml, p<0.01). Significant positive correlation has been found between VCAM-1 level and IL-6 content in blood plasma: r =0.25, p<0.05. CHD patients - L162V genotype carriers of PPAR-α gene - have revealed elevated VCAM-1 level of blood plasma compared to patients - L162L genotype carriers ­­(1054+129 ng/ml and 965+48 ng/ml respectively, p<0.05). IL-8 content in CHD patients with L162V genotype was higher than in L162L genotype carriers and healthy people - 2208+90.4 pkg/ml, 484.0+57.2 pkg/ml (p<0.001) and 472.1+128 pkg/ml (p<0.001) respectively. IL-8 content in CHD patients with G603G TF gene genotype were higher, than in A603A genotype carriers (981,3±214 pkg/ml and 308,1±59,2 pkg/ml respectively, p<0,05) The same tendencies were revealed in IFN-γ plasma content (1,58±0,251 pkg/ml in G603G tissue factor gene carriers and 0,99±0,205 pkg/ml in A603A genotype carriers. Conclusions. L162V PPAR-α and G603G tissue factor gene genotypes are associated with elevated levels of endothelial dysfunction markers in coronary heart disease patients in Russian population.