Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis

Mol Cell Biochem. 2012 Nov;370(1-2):241-9. doi: 10.1007/s11010-012-1419-3. Epub 2012 Aug 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Angiography
  • Coronary Restenosis / blood
  • Coronary Restenosis / diagnostic imaging
  • Coronary Restenosis / etiology
  • Coronary Restenosis / genetics*
  • Erythrocytes / enzymology
  • Free Radicals / metabolism*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Glutathione Peroxidase / blood
  • Glutathione Peroxidase / genetics*
  • Glutathione Peroxidase GPX1
  • Humans
  • Lipid Peroxides / metabolism
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Stents / adverse effects*

Substances

  • Free Radicals
  • Lipid Peroxides
  • Glutathione Peroxidase
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Glutathione Peroxidase GPX1
  • GPX1 protein, human