Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis.
Our aim was to examine correlations between polymorphisms in five antioxidant enzymes genes, activity of free-radical processes, and the risk of restenosis after coronary artery stenting with bare metal stents (BMS). A total of 101 male patients who underwent intracoronary stenting using BMS and coronary angiography follow-up of 6 months were enrolled in: group with in-stent restenosis (n = 44) and without restenosis (n = 57). The content of lipoperoxides and malondialdehyde (MDA) in Low-density lipoprotein (LDL), activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) in erythrocytes, and genotypes polymorphisms of the CAT gene (-262C/T), paraoxonase-1 (PON-1) gene (163T/A and 575A/G), endothelial nitric oxide synthase (eNOS) gene (298G/T (rs#1799983) and -786T/C), GPx-1 gene (599C/T (rs#1050450)), and glutathione-S-transferase (GSTP) gene (313A/G) were determined. In carriers of the minor allele of 599C/T polymorphism of the GPx-1 gene, activity of GPx in erythrocytes was lower by 17 % than in wild allele homozygotes, while the content of lipoperoxides in LDL was higher by 74 %. T-allele of 599C/T polymorphism of the GPx-1 gene (OR = 2.9; 95 % CI: 1.23-6.82) and T-allele of 298G/T polymorphism of the eNOS gene (OR = 2.79; 95 % CI: 1.17-6.66) were associated with the risk of in-stent restenosis. Minor alleles of polymorphisms 298G/T of the eNOS gene and 599C/T of the GPx-1 gene are associated with an increased risk of in-stent restenosis. Minor allele of the GPx-1 gene 599C/T polymorphism leads to a decrease of the GPx activity and increase of the activity of free-radical processes.
Department of Atherosclerosis Problems, Russian Cardiology Research and Production Complex of the Russian Federation Ministry of Health and Social Development, Moscow, Russia. shuvalovaj@mail.ru
Yu A
YA
Shuvalova
A I
AI
Kaminnyi
A N
AN
Meshkov
R O
RO
Shirokov
A N
AN
Samko
D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology; D005609:Free Radicals / Q000378:metabolism*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015607:Stents / Q000009:adverse effects*; D000094765:Glutathione Peroxidase GPX1
D005609:Free Radicals; D008054:Lipid Peroxides; D005979:Glutathione Peroxidase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human