Dataset Information

Evaluation of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and susceptibility to type 2 diabetes mellitus, a meta-analysis.

ABSTRACT: It is well established that type 2 diabetes mellitus (T2DM) is associated with oxidative stress and glutathione S-transferases (GSTs) protect cells against oxidative stress. The missense substitution Ile105Val (rs1695) of the glutathione S-transferase P1 (GSTP1, OMIM: 134660) results from an A/G base substitution at nucleotide 313. Many studies have evaluated the correlation between the rs1695 polymorphism and T2DM, but the results remain inconclusive. The aim of the present meta-analysis was to investigate the association between GSTP1 Ile105Val polymorphism and the susceptibility risk of T2DM. Eligible studies (published before August 2017) were identified in several databases. The heterogeneity between studies was evaluated with the chi-square based Q test and the I2 test. The strengths of the association were assessed by pooled odds ratios (ORs) and the corresponding 95 % confidence interval (95 % CI) using either a fixed or random-effects models. Eighteen studies documenting a total of 2595 T2DM cases and 2888 controls were included in this meta-analysis. In the overall analysis there was no significant association between the rs1695 polymorphism and the risk of T2DM. The subgroup analyses stratified by ethnicity, publication year and sample size did not reveal significant association between the study polymorphism and the risk of T2DM and any sources contributing to the substantial heterogeneity between studies. The present meta-analysis suggested that there was significant heterogeneity between studies. Considering some limi tations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

SUBMITTER: Saadat M

PROVIDER: S-EPMC5735339 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Evaluation of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and susceptibility to type 2 diabetes mellitus, a meta-analysis.

Saadat Mostafa M

EXCLI journal 20171106

It is well established that type 2 diabetes mellitus (T2DM) is associated with oxidative stress and glutathione S-transferases (GSTs) protect cells against oxidative stress. The missense substitution Ile105Val (rs1695) of the glutathione S-transferase P1 (GSTP1, OMIM: 134660) results from an A/G base substitution at nucleotide 313. Many studies have evaluated the correlation between the rs1695 polymorphism and T2DM, but the results remain inconclusive. The aim of the present meta-analysis was to ...[more]

PMID: 29285015

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Project description:Glutathione S-transferase P1 is a Phase II cytoprotective and detoxifying enzyme that is widely expressed in human airways. The glutathione S-transferase P1 Ile105Val polymorphism has been linked with atopic disorders and asthma. Yet, little remains known about the regulation of allergic inflammation by glutathione S-transferase P1 in human asthmatics.To establish the effect of the glutathione S-transferase P1 Ile105Val polymorphism on allergen-induced airway inflammation and oxidant stress, and non-specific bronchial hyperresponsiveness to methacholine and reactivity to specific allergen in mild human atopic asthmatics in vivo.Five Val(105)/Val(105) , twelve Val(105)/Ile(105) and twenty Ile(105)/Ile(105) mild atopic asthmatics underwent methacholine challenge, inhaled allergen challenge and endobronchial allergen provocation through a bronchoscope. A panel of inflammatory cytokines and chemokines, F2 -isoprostanes and isofuranes, markers of oxidative stress, thromboxane B2 and immunoglobulin E were measured in bronchoalveolar lavage fluid at baseline and 24 h after allergen instillation.Asthmatics with glutathione S-transferase P1 Val(105)/Val(105) compared with asthmatics with the glutathione S-transferase P1 Val(105)/Ile(105) and Ile(105)/Ile(105) had greater generation of acute phase cytokines (TNF-?, IL-6, CXCL8), IL-12, CCL11, thromboxane B2 and immunoglobulin E at 24 h after local allergen challenge. The GSTP1 genotype had no effect on airway hyperresponsiveness to methacholine and the reactivity to specific allergen.The glutathione S-transferase P1 Ile105Val polymorphism markedly modifies allergen-provoked airway inflammation in atopic asthmatics in vivo. Modulation of the biochemical milieu in response to allergen provides a mechanistic explanation for regulatory effects of glutathione S-transferase P1 polymorphism on airway pathophysiology, and may guide improvement of future therapeutic methods in human atopic asthmatics. These findings must me confirmed in a larger study population of asthmatics with various ethnicities.

Project description:BackgroundAnti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most common adverse effects associated with tuberculosis (TB) therapy. Animal studies have demonstrated important roles of glutathione S-transferases in the prevention of chemical-induced hepatotoxicity. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of glutathione S-transferase P1 (GSTP1) and ATDH in TB patients.MethodsWe used two independent samples for this genetic association study. In the initial prospective study, 322 newly diagnosed TB patients were followed up for three months after initiating anti-TB therapy. In an independent retrospective study, 115 ATDH patients and 116 patients without ATDH were selected to verify the results of the prospective study. Tag-SNPs of GSTP1 were genotyped either with the MassARRAY platform or the improved multiple ligase detection reaction (iMLDR) method. The associations between SNPs and ATDH were analyzed by logistic regression analysis adjusting for confounding factors.ResultsOf the 322 patients recruited in the prospective cohort, 35 were excluded during the 3 months of follow-up, and 30 were diagnosed with ATDH and were considered as the ATDH group. The remaining 257 subjects without ATDH were considered as the non-ATDH group. After correction for potential confounding factors, significant differences were found for rs1695 (A>G) under an allelic model (OR = 3.876, 95%CI: 1.258011.905; P = 0.018). In the retrospective study, rs1695 allele A also had a higher risk of ATDH (OR = 2.10, 95%CI: 1.17-3.76; P = 0.012). We only found rs4147581AA genotype under a dominant model was related to ATDH in the prospective study (OR = 2.578, 95%CI: 1.076-6.173; P = 0.034).ConclusionsThis is the first study to suggest that GSTP1 genotyping can be an important tool for identifying patients who are susceptible to ATDH. This result should be verified in independent large sample studies and also in other ethnic populations.

Dataset Information

Evaluation of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and susceptibility to type 2 diabetes mellitus, a meta-analysis.

Publications

Evaluation of glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and susceptibility to type 2 diabetes mellitus, a meta-analysis.

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