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

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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.

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Acknowledgments

This work was supported by a grant of Russian Foundation for Basic Research (06-04-49691-a). We thank Dr. Vadim Z. Lankin and Dr. Alla K. Tikhaze for their support of some biochemistry research.

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Authors and Affiliations

  1. Department of Atherosclerosis Problems, Russian Cardiology Research and Production Complex of the Russian Federation Ministry of Health and Social Development, 3rd Cherepkovskaya Street, 15a, Moscow, 121552, Russia

    Yu. A. Shuvalova & A. I. Kaminnyi

  2. Department of Clinical Cardiology and Molecular Genetics, National Center of Preventive Medcine, Moscow, Russia

    A. N. Meshkov

  3. Laboratory of Radio Vascular Therapy, Russian Cardiology Research and Production Complex of the Russian Federation Ministry of Health and Social Development, Moscow, Russia

    R. O. Shirokov & A. N. Samko

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  1. Yu. A. Shuvalova
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Correspondence to Yu. A. Shuvalova.

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Shuvalova, Y.A., Kaminnyi, A.I., Meshkov, A.N. et al. Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis. Mol Cell Biochem 370, 241–249 (2012). https://doi.org/10.1007/s11010-012-1419-3

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