Influence of genetic polymorphisms in oxidative stress related genes and smoking on plasma MDA-LDL, soluble CD40 ligand, E-selectin and soluble ICAM1 levels in patients with coronary artery disease.

Background: Previous studies have shown that oxidative stress plays an important role in coronary heart disease. Polymorphisms in key enzymes that regulate oxidative stress may play a role in atherogenicity and were investigated in this study.

Material/methods: One hundred and forty-three patients with angiographically proven coronary artery disease were studied. The effect of the C242T polymorphism of the p22phox gene, an essential component of the NADH/NADPH oxidase, and glutathione-S-transferase T1, M1 and P1 polymorphisms on plasma MDA-LDL, soluble CD40 ligand, E-selectin and soluble ICAM1 levels was determined. Genotyping of the p22 phox C242T polymorphism was performed by RFLP analysis, and GSTT1, GSTM1 and GSTP1 genotypes were determined using a multiplex PCR assay. The MDA-LDL, sCD40L, E-selectin and sICAM1 levels were determined using ELISA.

Results: Patients with the TT or TC genotype of the p22 phox C242T polymorphism had significantly higher plasma MDA-LDL levels compared to those of the CC genotype. Plasma E-selectin and soluble ICAM1 levels were significantly higher in the TT or TC genotype compared to that of the CC genotype. In GSTT1+ patients, plasma MDA-LDL levels were significantly higher than those of GSTT1- patients.

Conclusions: Genetic polymorphism of the p22 phox gene had a significant effect on plasma lipid peroxidation and endothelial function through oxidative stress. The results of this study confirm the effect of NADH/NADPH oxidase on atherogenecity.