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内皮型一氧化氮合酶和谷胱甘肽过氧化物酶-1 基因多态性与自由基过程活性和支架内再狭窄的关系。

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

机构信息

Department of Atherosclerosis Problems, Russian Cardiology Research and Production Complex of the Russian Federation Ministry of Health and Social Development, Moscow, Russia.

出版信息

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.

摘要

我们的目的是研究五种抗氧化酶基因的多态性、自由基过程的活性与冠状动脉内支架置入术后裸金属支架(BMS)再狭窄的风险之间的相关性。共纳入 101 名男性患者,这些患者接受了 BMS 冠状动脉内支架置入术,并且进行了 6 个月的冠状动脉造影随访:支架内再狭窄组(n=44)和无再狭窄组(n=57)。低密度脂蛋白(LDL)中脂质过氧化物和丙二醛(MDA)的含量、超氧化物歧化酶(SOD)、红细胞过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)的活性,以及 CAT 基因(-262C/T)、对氧磷酶-1(PON-1)基因(163T/A 和 575A/G)、内皮型一氧化氮合酶(eNOS)基因(298G/T(rs#1799983)和-786T/C)、GPx-1 基因(599C/T(rs#1050450))和谷胱甘肽-S-转移酶(GSTP)基因(313A/G)的基因型多态性。在 GPx-1 基因 599C/T 多态性的次要等位基因携带者中,红细胞 GPx 的活性比野生型纯合子低 17%,而 LDL 中的脂质过氧化物含量高 74%。GPx-1 基因 599C/T 多态性的 T 等位基因(OR=2.9;95%CI:1.23-6.82)和 eNOS 基因 298G/T 多态性的 T 等位基因(OR=2.79;95%CI:1.17-6.66)与支架内再狭窄的风险相关。eNOS 基因 298G/T 和 GPx-1 基因 599C/T 多态性的次要等位基因与支架内再狭窄的风险增加相关。GPx-1 基因 599C/T 多态性的次要等位基因导致 GPx 活性降低和自由基过程活性增加。

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