Glutathione S-transferase T1 Polymorphisms Research Articles

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio=2.04, 95% CI=1.30-3.20, P=0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio=2.90, 95% CI=1.43-5.87, P=0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk: A meta-analysis and re-analysis of systematic meta-analyses.

Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk.We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems.Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses.Significantly increased LC risk was considered as “highly credible” or “positive” for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17–1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12–1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16–1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17–1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as “highly credible” or “positive” in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22–1.48, I2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17–1.58, I2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype.This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

Role of Glutathione-S-Transferases in Gallbladder Cancer and Cholelithiasis Susceptibility and Meta-Analysis

Glutathione-S-transferase T1 (GSTT1) and glutathione-S-transferase M1 (GSTM1) genes are associated with increase susceptibility to developing different types of cancers. The aim of present study was to investigate the role of genetic variants of GSTM1 and GSTT1 in gallbladder cancer (GBC) and cholelithiasis in Kashmir valley. Genotyping was done by multiplex polymerase chain reaction in 100 GBC, 100 cholelithiasis, and 150 controls adjusted by age and sex. We also performed a meta-analysis of published studies on GSTM1 and GSTT1 to evaluate the association between the GSTM1 and GSTT1 polymorphisms and GBC. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. In the present study, no association was observed between GSTM1 null and GSTT1 null genotypes and GBC and cholelithiasis. Meta-analysis results showed that GSTM1 null genotype was associated with GBC risk (P = 0.042). Subgroup analysis by ethnicity showed that GSTM1 null (P = 0.024) and GSTT1 null genotype (P = 0.037) were significantly associated with risk of GBC in Asians. This is the first study to investigate the role of genetic variants of GSTM1 and GSTT1 in GBC in Kashmir valley and cholelithiasis in the world.

Combined effects of GSTM1 and GSTT1 polymorphisms on breast cancer risk: A MOOSE-compliant meta-analysis and false-positive report probabilities test.

Many molecular epidemiology studies have reported an association between the combined effects of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms on breast cancer risk. However, the results have been controversial.A meta-analysis was performed to clarify this issue.Meta-analysis of observational studies in epidemiology guidelines was used. Pooled the crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model or fixed-effects model. Several subgroup analyses were conducted by ethnicity, source of control, matching, and menopausal status. In addition, we also performed sensitivity analysis and publication bias. Moreover, a false-positive report probability (FPRP) test was applied to assess positive results.A significantly increased breast cancer risk was observed in overall population (GSTM1 null/GSTT1 present [− +] vs GSTM1 present/GSTT1 present [+ +]: OR = 1.19, 95% CI: 1.03–1.36, GSTM1 null/GSTT1 null [− −] vs + +: OR = 1.63, 95% CI: 1.29–2.06, (− +) + GSTM1 present/GSTT1 null (+ −) vs + +: OR = 1.17, 95% CI: 1.05–1.31, (− +) + (+ −) + (− −) vs + +: OR = 1.27, 95% CI: 1.12–1.44, and − − vs (− +) + (+ −) + (+ +): OR = 1.39, 95% CI: 1.17–1.66) and several subgroup analyses, such as Caucasians, Indians, postmenopausal women, and so on. However, positive results were only considered noteworthy in overall population (− − vs + +: FPRP = 0.150 and (− +) + (+ −) + (− −) vs + +: FPRP = 0.162). Moreover, no significant association was observed when we used the trim and fill method to adjust the pooled data from all populations. Further, none of positive results of sensitivity analysis were considered noteworthy (FPRP >0.2).These positive findings should be interpreted with caution and indicate that an increased breast cancer risk may most likely result from false-positive results, rather than from true associations or biological factors on the combined effects of GSTM1 and GSTT1. Future studies should be based on sample sizes well-powered and attention needs to be paid to study design to further identify this issue.

Glutathione S-transferase gene polymorphisms and risk of nasal or colorectal polyposis.

We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase pi (GSTP1) Ile105Val polymorphisms, in the susceptibility to nasal or colorectal polyposis (NP or CP). Thus, we aimed to perform a meta-analysis to comprehensively evaluate this association by applying Stata/SE software. After the heterogeneity assumption, Mantel–Haenszel statistics were used to obtain the odds ratio (OR), 95% confidence interval (95% CI) and P-value of the association test (PA). We obtained a total of 235 articles by searching online databases. After screening, ten eligible case–control studies were finally enrolled in our meta-analysis. For the meta-analysis of the GSTT1 gene under present versus null, we observed a decreased risk of NP [OR = 0.65; PA=0.018], but not CP. In addition, we did not detect any evident association between the GSTM1 present/null polymorphism and NP or CP risk. For the meta-analysis of the GSTP1 Ile105Val polymorphism, compared with controls, an increased risk of NP cases was detected under the models of Val versus Ile (OR = 1.36; PA=0.027), Ile/Val versus Ile/Ile (OR = 1.70; PA=0.011) and Ile/Val+Val/Val versus Ile/Ile (OR = 1.65; PA=0.010). In conclusion, the null genotype of the GSTT1 polymorphism may be linked to an increased susceptibility to NP, whereas the Ile/Val genotype of the GSTP1 Ile105Val polymorphism may be associated with a decreased risk of NP.

GSTT1 Null Genotype and Susceptibility to Children Acute Leukemia in Chinese Population: Evidence from a Meta-Analysis

Objectives:Increasing number of studies has focused on studying the relationship between glutathione S-transferase T1 polymorphism and children acute leukemia, among which discrepancies have risen. The aim of this study is to provide a more exact assessment of glutathione S-transferase T1 polymorphism and children acute leukemia among certain Chinese population.Methods:Studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine from beginning to July 2018. The strength of association was quantified by pooling odds ratios and 95% confidence intervals using fixed-effect or random-effect model according to the heterogeneity.Results:Overall, a positive relationship was found in null genotype of glutathione S-transferase T1 polymorphism on the risk of childhood acute leukemia among all Chinese populations (odds ratios: 1.52; 95% confidence intervals = 1.19-1.94). Similarly, consistent results were found in subgroup of Southern China (odds ratios: 1.48; 95% confidence intervals: 1.08-2.02), Northern China (odds ratios: 1.59; 95% confidence intervals: 1.09-2.33), acute lymphoblastic leukemia (odds ratios: 1.61; 95% confidence intervals: 1.19-2.17), “age > 18 years” (odds ratios: 1.59; 95% confidence intervals: 1.09-2.33), “age < 18 years” (odds ratios: 1.48; 95% confidence intervals: 1.08-2.02), and population-based studies (odds ratios: 1.60; 95% confidence intervals: 1.16-2.20).Conclusions:Collectively, finding from the current study indicated that GSTT1 null polymorphism may be susceptible on childhood acute leukemia among Chinese.

Glutathione S-transferase M1 and T1 polymorphisms, and their interactions with smoking on risk of low birth weight: a meta-analysis

Background: Published data regarding the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) gene polymorphisms and risk of low birth weight (LBW) remains inconclusive, and data on the interactions between the two gene polymorphisms and smoking for LBW susceptibility is lacking. To clarify these associations, a meta-analysis was conducted.Methods: A comprehensive literature search was conducted in multiple databases until 11 January 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random effects model.Results: Thirty-eight studies from 17 articles concerning maternal and neonatal GSTM1 and GSTT1 gene polymorphism with LBW risk were included in this meta-analysis, and nine studies from five articles provided data of maternal tobacco exposure status during pregnancy. Maternal GSTM1 null genotype was associated with increased LBW risk (OR = 1.27, 95% CI: 1.12–1.45). There was a nonsignificant but positive association (OR = 1.19, 95% CI: 0.97–1.46) between the maternal GSTT1 null genotype and the LBW risk in the overall analysis. There was a null association between neonatal GSTM1 or GSTT1 polymorphism and LBW risk. There were significant associations between the maternal GSTM1 null and GSTT1 null genotype and LBW risk (for the former, OR = 3.85, 95% CI: 1.68–8.81; for the later, OR = 1.88, 95% CI: 1.01–3.50) in individuals with active smoking, respectively.Conclusion: Maternal GSTM1 and GSTT1 null genotypes, but not neonatal genotypes, are suggested to increase LBW susceptibility, and there are interactions between active smoking and these polymorphisms in the development of LBW.

Glutathione S-transferase M1 and T1 null genotypes and bladder cancer risk: A meta-analysis in a single ethnic group.

To further evaluate the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null genotypes on bladder cancer risk, we conducted a meta-analysis in the Chinese population. PubMed and Chinese databases were electronically searched through April 2016. Nine studies were included for our meta-analysis, involving 1646 bladder cancer cases and 1938 controls. In general, our findings indicated that a significant association existed between GSTM1-null genotype and the risk of bladder cancer in the studied Chinese population (odds ratio = 1.56, 95% confidence interval: 1.36-1.79). However, no significant association between GSTT1 polymorphism and bladder cancer was found. After stratification of the subgroup analyses by source of controls and geographical areas, a substantially elevated risk was revealed between GSTM1-null genotype and bladder cancer in the population-based studies and those conducted in South China and North China. Our meta-analysis suggested that GSTM1-null genotype is associated with an increased bladder cancer risk in the Chinese individuals.

The Impacts of Cord Blood Cotinine and Glutathione-S-Transferase Gene Polymorphisms on Birth Outcome

This study aimed to investigate the association between cord blood cotinine levels and birth outcome, and to determine whether fetal metabolic gene polymorphisms of glutathione-S-transferase (GST) modulate the effect of environmental tobacco smoke exposure during pregnancy. This study included 328 maternal and neonatal pairs. Maternal and cord blood cotinine levels were measured using high performance liquid chromatography. The GST T1 (GSTT1) and GST M1 (GSTM1) polymorphisms were examined using the polymerase chain reaction method. The birth outcomes included birth weight, length, and head circumference, and the risks of having low birth weight and being small for gestational age (SGA). Cord cotinine level had a dose-dependent impact on the reduction of birth weight, length, and head circumference in newborns. Elevation of cord blood cotinine concentration increased the rate of SGA and low birth weight. The neonates who had GSTT1 or GSTM1 polymorphism were associated with an increased risk of being SGA. A combination of the GSTT1 and GSTM1 null genotype exacerbated the effect of maternal environmental tobacco smoke exposure on SGA more than the presence of either genotype alone (odds ratio=8.90, 95% confidence interval=1.00-79.5). Cord blood cotinine adversely affects birth outcomes. GSTT1 and GSTM1 null genotype may modify the effect of cord blood cotinine on birth outcomes.

Oxidative stress markers and genetic polymorphisms of glutathione S-transferase T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos, Nigeria

The role of oxidative stress has been identified in the development of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase have been associated with some diseases linked to oxidative stress. Hence, we evaluated the serum levels of oxidative stress markers and investigated genetic polymorphisms of glutathione S-transferase associated with autism. Forty-two children clinically diagnosed with ASD using the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical interview were included in the study. Twenty-three age-matched controls without any known genetic/developmental disorder were also recruited. Oxidative stress markers along with the genetic polymorphisms of glutathione S-transferase were determined. Reduced glutathione in ASD patients was significantly lower than the control (P = 0.008), whereas other oxidative stress markers measured were not significantly different in both the control and case populations. The frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls compared with the cases, however, no association risk was observed. The observed risk of carrying Val/Val genotype among the cases was approximately six times that of the controls. Individuals with ASD showed a significant diminished level of reduced glutathione, however, the distribution of GSTT1, GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this study population.

Association of glutathione S-transferase polymorphisms with the severity of mustard lung

Introduction: Glutathione S-transferase (GST) is one of the major detoxifiers in alveoli. Polymorphism in GST genes can influence the ability of individuals to suppress oxidative stress and inflammation. The present study was aimed to explore the hypothesis that the genetic polymorphisms of GST T1, M1 and P1 are associated with the severity of the mustard lung in the sulfur mustard-exposed individuals. Methods: Blood samples were taken from 185 sulfur mustard-exposed and 57 unexposed subjects. According to the stage of the mustard lung, sulfur mustard-exposed patients were categorized in the mild/moderate and severe/very severe groups. A multiplex PCR method was conducted to identify GSTM1 and GSTT1 null genotypes. To determine the polymorphisms of GSTP1 in exon 5 (Ile105Val) and exon 6 (Ala114Val), RFLP-PCR method was performed. Results: The frequency of GSTM1 homozygous deletion was significantly higher in the severe/very severe patients compared with the mild/moderate subjects (66.3% vs. 48%, P = 0.013). The GSTM1 null genotype was associated with the severity of mustard lung (adjusted odds ratio [OR], 2.257; 95% CI, 1.219-4.180). There was no significant association between GSTT1 and GSTP1 polymorphisms with the severity of the mustard lung. Conclusion: The different distribution of GSTM1 null genotype in severe/very severe and mild/moderate groups indicated that the severity of the mustard lung might be associated with the genetic polymorphism(s).

Associations Among Glutathione S-Transferase T1, M1, and P1 Polymorphisms and the Risk of Oral Leukoplakia.

The potential association between glutathione S-transferase (GST) M1, T1, P1 polymorphisms and the risk of oral leukoplakia (OLK) has been extensively studied. However, the results of previous studies have been contradictory. In an effort to resolve these different findings we performed a meta-analysis. Eligible articles were identified by a search of PubMed, the China National Knowledge Infrastructure (CNKI), MEDLINE, EMBASE, and the Web of Science databases through December 1, 2015. Crude odds ratios (ORs) with 95% confidence intervals were used to evaluate the risk of OLK by tobacco use, ethnicity, and OLK subtype. A total of 3122 cases and 6037 controls were included in the meta-analysis. The results indicated that the glutathione S-transferase Mu1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms increase the risk of OLK (OR = 1.838, 95% CI = 1.582-2.134 and OR = 1.337, 95% CI = 1.132-1.579, respectively), especially in the groups with tobacco use (OR = 2.478, 95% CI = 2.032-3.020 and OR = 2.034, 95% CI = 1.486-2.783, respectively). Conversely the glutathione S-transferase P1 (GSTP1) polymorphism did not demonstrate a significant relationship with OLK risk (OR = 1.139, 95% CI = 0.900-1.442). The GSTM1 and GSTT1 null polymorphisms were identified as being significantly associated with an increased risk of OLK within the German and Indian populations: German subgroup (GSTM1: OR = 11.555, 95% CI = 7.465-17.884), Indian subgroup (GSTM1: OR = 1.333, 95% CI = 1.084-1.638; GSTT1: OR = 1.332, 95% CI = 1.057-1.679). Our findings provide evidence that the GSTT1 and GSTM1 null polymorphisms may be risk factors of OLK, especially for persons who use tobacco, whereas the GSTP1 polymorphism does not contribute to the development of OLK. Thus, detection of GSTT1 and GSTM1 null polymorphisms may be promising biomarkers for the OLK susceptibility.

Evaluation of Glutathione S-transferase T1 (GSTT1) deletion polymorphism on type 2 diabetes mellitus risk in a sample of Yazdian females in Yazd, Iran.

Background:There has been much interest in the role of free radicals and oxidative stress in the pathogenesis of diabetes mellitus (DM). The aim of this study was to assess the possible association between genetic polymorphisms of the glutathione S-transferase-mu (GSTT1) and the risk of the development of DM in a sample of Yazdian females in Yazd, Iran.Methods:This was a case-control study in which GSTT1 polymorphism was genotyped in 51 randomly selected DM patients and 50 randomly selected healthy controls among Yazdian females whose ages ranged from 40 to 70.Results:The frequencies of GSTT1 null genotype and GSTT1 present were 8 and 92%, respectively, in the control samples. In patients with type 2 diabetes (T2DM), the frequencies of GSTT1 null genotype and GSTT1 present were 14 and 86%, respectively. There were higher levels of triglycerides (TG), fasting blood sugar (FBS), total cholesterol (TC), low density lipoprotein (LDL), body mass index (BMI), and high density lipoprotein (HDL) in patients with GSTT1 null genotype than in patients with the GSTT1 present genotype.Conclusions:Our results indicated that the GSTT1 deletion polymorphism is a risk factor for T2DM. We did not determine any significant association between the GSTT1 null genotype and T2DM.

Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric carcinoma: a systematic review and meta-analysis

We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case-control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95% CI 1.06-1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95% CI 1.05-1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95% CI 1.01-1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95% CI 1.04-1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians.

Glutathione S-transferase T1 and myeloperoxidase -463 G>A genotypes in lung cancer patients of Kumaun region.

Background:Null genetic polymorphism of Glutathione S-transferase T1 (GSTT1) and -463 G>A promoter polymorphism of myeloperoxidase (MPO) were studied for association with lung cancer.Materials and Methods:In a case- control study 26 lung cancer patients and 33 healthy individuals from hilly Kumaun region of northern India were investigated. DNA was extracted from peripheral blood. GSTT1 null polymorphism was detected by duplex PCR, and MPO polymorphism was detected by performing PCR-RFLP.Results:An increased but statistically non- significant risk for lung cancer was found for GSTT1 null genotype. No association for MPO -463G>A genotype was evident.Conclusion:Further study with large sample size may reveal such association in this population.

Association between Glutathione S-transferase M1/Glutathione S-transferase T1 polymorphisms and Parkinson's disease: A meta-analysis

The Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) genes have been studied extensively as potential candidate genes for the risk of Parkinson's disease (PD). However, direct evidence from genetic association studies remains inconclusive. In order to address this issue, we performed an updated and refined meta-analysis to determine the effect of GSTM1 and GSTT1 polymorphisms on Parkinson's disease. A fixed-effect model was utilized to calculate the combined odds ratio (OR), OR of different ethnicities, and 95% confidence intervals (CIs). Potential publication bias was estimated. Homogeneity of the included studies was also evaluated. The pooled OR was 1.13 [95% CI (1.03, 1.24)] and 0.96 [95% CI (0.82, 1.12)] for GSTM1 and GSTT1 polymorphisms, respectively. Analysis according to different races found no association between GSTM1/GSTT1 polymorphisms and PD risks except for GSTM1 variant in Caucasians, which showed a weak correlation (OR 1.16 [95% CI (1.04, 1.29), I squared=6.2%, p=0.384]). Neither publication bias nor heterogeneity was found among the included studies. The results of this meta-analysis suggest that GSTM1 polymorphism is weakly associated with the risk of PD in Caucasians whereas GSTT1 polymorphism is not a PD risk factor.

Association between glutathione S-transferase T1 null genotype and risk of lung cancer: a meta-analysis of 55 studies

The relationship between glutathione S-transferase T1 (GSTT1) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 polymorphism and the risk of lung cancer. A comprehensive research was conducted through the databases, and 55 studies were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a significant association between GSTT1 null genotype and lung cancer risk in the overall populations (OR = 1.138, 95% CI = 1.032-1.255, P heterogeneity = 0.000, P = 0.009). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.469, 95% CI = 1.228-1.757, P heterogeneity = 0.000, P = 0.000). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.

Association between GSTP1, GSTM1, GSTT1 genetic polymorphisms and urinary styrene phenyl hydroxyethyl mercapturic acids level

To investigate the relationship between genetic polymorphisms of glutathione S-transferase P1 (GSTP1), glutathione S-transferase M1 (GSTM1), and glutathione S-transferase T1 (GSTT1) and urinary level of mercapturic acids of styrene (PHEMAs) in workers exposed to styrene. One hundred and twenty-six workers exposed to styrene were selected as exposure group, and 150 workers without styrene exposure as the control group; all the workers came from a locomotive shell production factory in Shandong Province, China. The PCR-RFLP technique was applied to analyze the individual genetic polymorphisms of GSTP1; the multiplex PCR technique was used to investigate the genetic polymorphisms of GSTM1 and GSTT1; the relationship between genetic polymorphisms of GSTP1, GSTM1, and GSTT1 and urinary level of PHEMAs in workers exposed to styrene was statistically analyzed. The three genotypes investigated in the study had a distribution in accordance with the Chinese population. With exposure to high- concentration styrene, the individuals carrying GSTP1 (exon5, A105G) AA genotype (wildtype) had a significantly higher urinary level of PHEMAs (43.58 mg/g) than those with mutant genotypes AG (29.769 mg/g) and GG (30.245 mg/g); the urinary level of PHEMAs in individuals carrying wild-type GSTM1 genotype was significantly higher than that in individuals carrying deficient-type GSTM1 genotype (40.197 mg/g vs 28.866 mg/g, P < 0.05); no significant difference in urinary level of PHEMAs was found between individuals carrying wild-type GSTT1 genotype and deficient-type GSTT1 genotype. There was no significant relationship between the three gene polymorphisms and urinary level of PHEMAs in the control group. The genetic polymorphisms of GSTP1 and GSTM1 may be related to urinary level of PHEMAs in workers exposed to styrene.

Meta-analysis: glutathione S-transferase T1 null allele is associated with gastric cancer risk

Allelic variant within genes encoding glutathione S-transferase T1 (GSTT1) has been suggested to be a possible risk factor of gastric cancer, but previous studies provide controversial results. This study aimed to assess the effects of GSTT1 polymorphism on gastric cancer by means of meta-analysis. We included published studies on the relationship between GSTT1 null allele and gastric cancer risk after searching electronic databases. A meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). Forty-two studies with a total of 8,203 gastric cancer cases and 13,866 controls were included into this meta-analysis. When all 42 studies were pooled into this meta-analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk (OR = 1.24, 95% CI 1.14-1.36, P < 0.00001). Sensitivity analysis by excluding individual studies showed that there was no effect on the pooled OR with 95% CI. After excluding studies with low quality, there was still a significant association between the GSTT1 null allele and gastric cancer risk (OR = 1.24, 95% CI 1.13-1.36, P < 0.00001). In the subgroup analysis, there was a significant association between the GSTT1 null allele and gastric cancer risk in both Europeans and Asians. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null allele is associated with increased risk of gastric cancer.

GSTT1 null genotype contributes to hepatocellular carcinoma risk: a meta-analysis

Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and hepatocellular carcinoma (HCC) risk have reported conflicting results. Therefore, we conducted this meta-analysis to provide more precise evidence. Databases including PubMed, Embase, SCOPUS, ISI Web of Science, and Wangfang were searched for relevant studies. Potential sources of heterogeneity were also assessed by subgroup analysis. Funnel plots and Egger's linear regression were used to test publication bias among the articles. Finally, a total of 28 studies involving 3,897 HCC patients and 6,117 controls were included in this meta-analysis. In a combined analysis, the summary odds ratio for HCC of the GSTT1 null genotype was 1.43 (95% confidence interval (CI) 1.22–1.68, P < 10(−5)). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for GSTT1 null polymorphism, while no significant associations were found among Caucasian, South Asian, and African populations. When stratified by a source of controls, both population- and hospital-based studies get consistent positive results. By pooling data from 10 studies (1,639 cases and 2,224 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for HCC (odd ratio = 1.85, 95% CI 1.37–2.49) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes. No evidence of publication bias was observed. Our result suggests that the GSTT1 null genotype contributes to an increased risk of HCC in East Asians and that interaction between unfavorable GSTs genotypes may exist.