谷胱甘肽S-转移酶O1（GSTO1）和谷胱甘肽S-转移酶O2（GSTO2）基因多态性与终末期肾病发生风险及患者生存率的关联

Association of GSTO1 and GSTO2 Polymorphism with Risk of End-Stage Renal Disease Development and Patient Survival.

作者信息

Cimbaljevic Slavica, Suvakov Sonja, Matic Marija, Pljesa-Ercegovac Marija, Pekmezovic Tatjana, Radic Tanja, Coric Vesna, Damjanovic Tatjana, Dimkovic Nada, Markovic Rodoljub, Savic-Radojevic Ana, Simic Tatjana

机构信息

Serbian Chamber of Biochemists.

Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

J Med Biochem. 2016 Sep;35(3):302-311. doi: 10.1515/jomb-2016-0009. Epub 2016 Jul 6.

DOI:10.1515/jomb-2016-0009

PMID:28356881

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5346808/

Abstract

BACKGROUND

Oxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients.

METHODS

A total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month).

RESULTS

Individuals carrying the variant genotype were at 2.45-fold higher risk of ESRD development compared to the wild type genotype (OR=2.45; 95%CI=1.18-5.07; p=0.016). The results of haplotype analysis showed that the haplotype combination of ()/ () ( variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least one reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122).

CONCLUSIONS

GSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients' survival.

摘要

背景

终末期肾病（ESRD）患者的氧化应激与长期心血管并发症相关。谷胱甘肽S-转移酶（GSTs）的胞质家族参与多种有毒化合物的解毒和抗氧化保护。与其他GSTs不同，GST omega亚类成员GSTO1和GSTO2具有脱氢抗坏血酸还原酶和去谷胱甘肽化活性。本研究的目的是阐明GSTO1（rs4925）和GSTO2（rs156697）基因多态性作为ESRD发生风险决定因素的作用，以及在这些患者生存中的作用。

方法

共纳入199例患者和199例健康受试者，对GSTO1和GSTO2多态性进行基因分型。采用分光光度法测定蛋白质巯基和羰基作为蛋白质氧化损伤的标志物。采用Cox比例风险模型和Kaplan-Meier分析，研究GSTO1和GSTO2基因多态性在随访期（36个月）对ESRD患者死亡率的作用。

结果

与野生型基因型相比，携带变异基因型的个体发生ESRD的风险高2.45倍（OR=2.45；95%CI=1.18-5.07；p=0.016）。单倍型分析结果显示，（）/（）（GSTO1变异/GSTO2野生型等位基因）的单倍型组合对ESRD具有保护作用（OR=0.23，95%CI=0.12-0.44，p=0.001）。携带至少一个GSTO1参考等位基因的患者的平均总生存期（对数秩检验=2.844，p =0.241）和心血管生存期概率较短（对数秩检验=4.211，p=0.122）。