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

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 polymorphism should 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.