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
Takahiro Ueno, Hideyuki Watanabe, Noboru Fukuda, Akiko Tsunemi, Kazunobu Tahira, Taro Matsumoto, Tadateru Takayama, Masaaki Chiku, Satoshi Saito, Yuichi Sato, Atsushi Hirayama, Koichi Matsumoto, Masayoshi Soma
Med Sci Monit 2009; 15(7): CR341-348
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 and Method: 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.
Keywords: Oxidative Stress - genetics, NADPH Oxidase - genetics, Middle Aged, Malondialdehyde - blood, Lipoproteins, LDL - blood, Intercellular Adhesion Molecule-1 - blood, Humans, Glutathione Transferase - genetics, Glutathione S-Transferase pi - genetics, E-Selectin - blood, Coronary Disease - genetics, CD40 Ligand - blood, Aged, Polymorphism, Genetic, Smoking - genetics, Solubility