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谷胱甘肽S-转移酶基因(GSTM1、GSTT1、GSTP1)的基因多态性对糖尿病肾病风险的影响:一项荟萃分析。

Effects of genetic polymorphisms of glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) on the risk of diabetic nephropathy: a meta-analysis.

作者信息

Orlewski Jan, Orlewska Ewa

出版信息

Pol Arch Med Wewn. 2015;125(9):649-58. doi: 10.20452/pamw.3045. Epub 2015 Aug 7.

Abstract

INTRODUCTION

Glutathione S-transferases (GSTs) belong to a family of ubiquitous and multifunctional enzymes that protect the cells against oxidative stress.

OBJECTIVES

The aim of the study was to evaluate the association between the polymorphisms of glutathione-S-transferase (GST) genes and diabetic nephropathy (DN).

PATIENTS AND METHODS

PubMed, EMBASE, and Google Scholar databases were systematically searched to identify relevant studies. The odds ratio (OR) for the association was determined using a fixed or random effects model. Tests for heterogeneity of the results and sensitivity analyses were performed.

RESULTS

A total of 9 publications (874 patients in the study group, 966 controls) were included. With the exception of 1 study, GSTT1 and GSTM1 genotypes were not assessed by methods that measure a gene copy number. A significantly increased risk of DN was found for the GSTM1(-) genotype (OR, 1.27; 95% CI, 1.02-1.58) and the combination of GSTT1(-)/GSTM1(-) (OR,2.02; 95% CI, 1.22-3.36). We did not observe a correlation between DN and the GSTT1(-) genotype or the presence of Val alleles. In a subgroup analysis, an association between DN and the GSTM1(-) genotype was significant in Asians but not in Caucasians.

CONCLUSIONS

Our results indicate that the GSTM1(-) genotype and the combination of GSTT1(-)/GSTM1(-) increase the risk of DN. The combination of the GST polymorphisms rather than individual polymorphismshould be investigated. Genotyping allowing a trimodular determination of the GST copy number variations may better describe an association between the risk of disease and a given genotype.

摘要

引言

谷胱甘肽S-转移酶(GSTs)属于一类普遍存在的多功能酶家族,可保护细胞免受氧化应激。

目的

本研究旨在评估谷胱甘肽S-转移酶(GST)基因多态性与糖尿病肾病(DN)之间的关联。

患者和方法

系统检索PubMed、EMBASE和谷歌学术数据库以识别相关研究。使用固定或随机效应模型确定关联的比值比(OR)。进行结果异质性检验和敏感性分析。

结果

共纳入9篇文献(研究组874例患者,对照组966例)。除1项研究外,GSTT1和GSTM1基因型未通过测量基因拷贝数的方法进行评估。发现GSTM1(-)基因型(OR,1.27;95%CI,1.02-1.58)以及GSTT1(-)/GSTM1(-)组合(OR,2.02;95%CI,1.22-3.36)的DN风险显著增加。我们未观察到DN与GSTT1(-)基因型或Val等位基因的存在之间存在相关性。在亚组分析中,DN与GSTM1(-)基因型之间的关联在亚洲人中显著,但在白种人中不显著。

结论

我们的结果表明,GSTM1(-)基因型以及GSTT1(-)/GSTM1(-)组合会增加DN风险。应研究GST多态性的组合而非单个多态性。允许对GST拷贝数变异进行三模块测定的基因分型可能更好地描述疾病风险与特定基因型之间的关联。

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