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<0.01. In the group of patients with BMI >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.