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.


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.
Ueno
Takahiro
T
Department of Medicine, Division of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo, Japan. tueno@med.nihon-u.ac.jp
Watanabe
Hideyuki
H
Fukuda
Noboru
N
Tsunemi
Akiko
A
Tahira
Kazunobu
K
Matsumoto
Taro
T
Takayama
Tadateru
T
Chiku
Masaaki
M
Saito
Satoshi
S
Sato
Yuichi
Y
Hirayama
Atsushi
A
Matsumoto
Koichi
K
Soma
Masayoshi
M
D000368:Aged; D023201:CD40 Ligand / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D019040:E-Selectin / Q000097:blood; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008315:Malondialdehyde / Q000097:blood*; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000097:blood* / Q000235:genetics; D012995:Solubility
D023201:CD40 Ligand; D019040:E-Selectin; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D018799:Intercellular Adhesion Molecule-1; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D019255:NADPH Oxidases; C086986:CYBA protein, human; C413545:glutathione S-transferase T1