Individual and combined effects of the GSTM1, GSTT1, and GSTP1 polymorphisms on type 2 diabetes mellitus risk: A systematic review and meta-analysis

Abstract

Backgrounds: Compared with previously published meta-analyses, this is the first study to investigate the combined effects of glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1 IIe105Val) and type 2 diabetes mellitus (T2DM) risk; moreover, the credibility of statistically significant associations was assessed; furthermore, many new original studies were published.Objectives: To determine the relationship between GSTM1, GSTT1, and GSTP1 polymorphisms with T2DM risk.Methods: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure Databases were searched. We quantify the relationship using crude odds ratios and their 95% confidence intervals Moreover, the Venice criteria, false-positive report probability (FPRP), and Bayesian false discovery probability (BFDP) were used to validate the significance of the results.Results: Overall, significantly increased T2DM risk was found between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on T2DM risk, but, combined effects of the GSTT1 and GSTP1 polymorphisms was not statistically significant. GSTT1 gene polymorphism significantly increases the risk of T2DM complications, while GSTM1 and GSTP1 polymorphisms had no statistical significance. The GSTM1 null genotype was linked to a particularly increased risk of T2DM in Caucasians; the GSTT1 null genotype was connected to a significantly higher risk of T2DM in Asians and Indians; and the GSTP1 IIe105Val polymorphism was related to a substantially increased T2DM risk in Indians. Moreover, the GSTM1 and GSTT1 double null genotype was associated with substantially increased T2DM risk in Caucasians and Indians; the combined effects of GSTM1 and GSTP1 polymorphisms was associated with higher T2DM risk in Caucasians. However, all significant results were false when the Venice criteria, FPRP, and BFDP test were used (any FPRP >0.2 and BFDP value >0.8).Conclusion: The current analysis strongly suggests that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms might not be connected with elevated T2DM risk.

Polygenic Variants Linked to Oxidative Stress and the Antioxidant System Are Associated with Type 2 Diabetes Risk and Interact with Lifestyle Factors

“…Although the genes found in the present study have been reported to be linked to T2DM risk in earlier studies [16,18], their genetic variants were not reported. Since many genetic variants are closely linked to each other, showing high LD (D' > 0.3), their genetic variants might be comparable to those reported in earlier studies [14,16].…”

“…Earlier studies suggested that oxidative stress is linked to genetic and environmental factors, and their interaction results in the development of T2DM and its complications. The oxidative stress-related genetic variants of GPX1 , GPX3 , glutathione S-transferase ( GST )-theta-1 (GSTT1) , GST-mu1 (GSTM1) , arachidonate 5-lipoxygenase (ALOX5), and cytochrome β-245 alpha chain (CYBA) have been found to influence T2DM risk [ 6 , 17 , 18 ]. However, these studies were conducted in small groups of participants, and genetic variants related to oxidative stress and antioxidant systems have yet to be studied in larger populations.…”

Glutathione S-Transferase P1 Genetic Variant’s Influence on the HbA1c Level in Type Two Diabetic Patients

“…This highlights that oxidative stress is a potential covariate in predicting patient response to antidiabetic treatment, and GSTP1 genotyping can be relevant for better identification of T2D patients who are likely to need specific pharmacological strategies focusing not only on lowering glucose [29], but also on oxidative stress. Many studies showed that Val allele of the GSTP1 Ile105Val polymorphism and the GSTP1 Val/Val genotype play an important role in individual susceptibility to T2D in different populations [4,[30][31][32][33][34][35], but only one study investigated the relationship between GSTP1 gene polymorphism and HbA1c level in T2D patients [31]. This study demonstrated no effect of polymorphism in the GSTP1 gene on glycemic control parameters, but in the population included in this study (n = 300) the GSTP1105Val/Val genotype, which significantly influenced the level of HbA1C in the Polish diabetic population, has not been detected.…”