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

Influence of GSTM1, GSTT1 and GSTP1 gene polymorphisms on the appearance of microalbuminuria in type 2 diabetes mellitus patients

“…The GSTT1 null genotype was not associated with DN even after stratified analysis was performed based on ethnicity, T2DM presence, sample size or presence of diabetic retinopathy. No correlation between the GSTP1 genotype and DN was found in the overall or subgroups analysis published by J. Orlewski et al [7]. However, authors mentioned that the data obtained must be carefully interpreted due to a large number of confounding factors, the relatively small number of patients included in each study, the ethnic heterogeneity and they consider that further investigations are required for exploring the correlation of the above-mentioned polymorphisms with the risk of DN.…”

“…GSTM1 null and GSTT1 null genotype combinations which are followed by a complete lack of enzymatic activity have not been associated with an increased risk of either diabetic retinopathy or nephropathy [10]. A pertinent meta-analysis regarding the effect of GSTs (GSTM1, GSTT1, and GSTP1) gene polymorphisms on the risk of DN that analyzed 9 publications and included 874 patients with T1DM and T2DM in the study group and 966 in the control group was published in 2015 by J. Orlewski et al [7]. This meta-analysis showed that the GSTM1 null genotype was statistically correlated with the risk of DN in Asians, but not in Caucasians; also, when only T2DM patients were analyzed no statistically significant correlation was found between the GSTM1 null genotype and DN.…”

“…The risk for albuminuria is more importantly correlated with the degree of the glycemic imbalance and the evolution of DM time, but a familial susceptibility also exists, which supports the role of genetic factors in the ethiopathogeny of DN. Probably, there is a high number of allelic variants that interact, and together with environmental factors and a metabolic imbalance they could generate an individual susceptibility regarding the relative risk of DN occurrence [7]. Oxidative stress is recognized as a causative…”

Association of Angiotensin-Converting Enzyme (ACE) and Glutathione S-Transferase (GST) Gene Polymorphisms with Diabetic Nephropathy

“…Studies in the area of diabetic nephropathy are not only few but also inconsistent in their results. While Fujita etal (18) found no association of GSTM1 deletion with diabetic nephropathy in Japanese T2DM patients and Orlewski J et al (22) also found the same in Poland ethnicity; Yang etal (23) showed that GSTT1 null genotype was a risk factor for development of diabetic nephropathy in the Chinese. Kim et al (16) found that GSTM1 null genotype is associated with development of nephropathy in Type 2 diabetes in the Korean population (table 1).…”

The Effect of Nrf2 on Diabetic Complications

“…Oxidative stress contributes to the pathogenesis of diabetic nephropathy. Nuclear factor erythroid-derived 2-like 2 (NRF2) controls cellular defense mechanisms against oxidative stress by turning on transcription of antioxidant genes [33]. Under physiological conditions Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and sequesters it in the cytoplasm.…”