Glutathione S-transferase M1 Gene Research Articles

Association of Glutathione s-transferase M1 and T1 gene polymorphisms with the susceptibility to acquired sensorineural hearing loss: a systematic review and meta-analysis

Acquired sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), drug-induced hearing loss (DIHL) and sudden sensorineural hearing loss (SSHL), is one of the most common sensory deficits in humans. Several studies have reported that antioxidant gene glutathione s-transferase M1 and T1 (GST M1 and T1) polymorphisms have a close relationship with the susceptibility to acquired SNHL, but other articles have reported opposite results. This meta-analysis aims to identify whether an association exists between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Seventeen independent studies containing 1749 cases and 2018 controls were included. According to the I2 value of the heterogeneity test, random-effects model was selected to calculate the pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) and p values. The pooled ORs (95% CI, p-value) of GST M1 and T1 were 1.186(0.955–1.473, p = 0.122) and 1.107(0.841–1.458, p = 1.467), respectively. In addition, subgroup analyses according to the type of SNHL and ethnicity showed no relationship between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Our results suggest that no significant relationship was found between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL.

Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens.

Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries. This hospital-based case-control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel-Haenszel method. The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC. ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.

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, t1, and p1 gene polymorphism in exudative age-related macular degeneration: a preliminary report.

To elucidate whether the gene polymorphisms of glutathione S-transferase (GST) M1, T1, and P1 are associated with the development of exudative age-related macular degeneration. The authors genotyped 35 white patients with exudative age-related macular degeneration and 159 healthy controls. Genomic DNA from peripheral blood was examined using polymerase chain reaction and defined for the genetic polymorphisms of GST. No association was observed between GSTM1, GSTT1, and GSTP1 polymorphisms and age-related macular degeneration risk (p>0.05). The frequencies of the combination of the GSTM1 (null) and GSTP1 (mutant), GSTM1 (null), and GSTT1 (null) genotype polymorphisms in patients with exudative age-related macular degeneration differed greatly from those of the control group (p=0.001 OR [95% CI]: 7.70 [2.28-25.98] and p=0.007 OR [95% CI]: 3.88 [1.51-10.02], respectively). The present study suggests that the GSTM1 (null) and GSTT1 (null), GSTM1 (null), and GSTP1 (mutant) combinations may be a genetic risk factor for the development of exudative age-related macular degeneration. However, the potential role of GST polymorphisms as a marker of susceptibility to age-related macular degeneration needs further studies in a larger number of patients. (Eur J Ophthalmol 2006; 16: 105-10).

Glutathione S-Transferase M1 and T1 Gene Deletions and Susceptibility to Acute Lymphoblastic Leukemia (ALL) in adults.

Objective:Biotransformation of xenobiotics are critical for their metabolism and removal from the body which is carried out by xenobiotic metabolizing enzymes. Individuals carrying variants of genes that encode these enzymes have an altered ability to metabolize xenobiotics which may lead to an increased risk of acute lymphoblastic leukemia. The current study aimed to investigate the impact of GSTM1 and GSTT1 gene deletions in causing predisposition to adult ALL.Methods:The current case-control study involved 62 adult ALL patients and 62 age and gender matched healthy controls. Whole blood samples processed with standard phenol chloroform protocol for DNA isolation were genotyped using multiplex PCR approach for simultaneous identification of GSTM1 and GSTT1 deletions. The genotype frequency obtained for patients was compared to controls using odds ratio and chi-square.Results:The null genotype frequency of GSTM1 and GSTT1 in a group of adult ALL patients from Pakistan were 47% and 11% respectively. Deletion of GSTM1 and GSTT1 did not show statistically significant association with adult ALL (p=0.86 and p=0.35 respectively). The combined GSTM1/GSTT1 deletion was observed in 2% patients and was not significantly associated with ALL in adults (p=0.85).Conclusions:The results reveal that homozygous null polymorphism of GSTM1 and GSTT1genes does not influence ALL susceptibility among adult patients. Cancer susceptibility associated with GST polymorphism varies with ethnic and geographic differences. Therefore, further investigation on different populations is needed to understand the role of these genetic variations in modifying adult ALL risk.

Polymorphism of glutathione S-transferase M1 and T1 genes and susceptibility to psoriasis disease: A study from North India.

Increased oxidative stress and resulting inflammation has been emphasized as a factor in the pathogenesis of many diseases including psoriasis. Glutathione S-transferases (GSTs) protect against oxidative stress, inflammation, and genotoxicity. Polymorphisms in the GST genes may lead to an imbalance in pro- and antioxidant systems resulting in the increased production of reactive oxygen species that could influence the pathogenesis of psoriasis. The aim of this study was to investigate the association between GSTs (GSTM1 and GSTT1) gene polymorphism in patients with chronic plaque psoriasis as a factor in the susceptibility and development of psoriasis. We assessed 128 patients with psoriasis and 250 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood by the phenol chloroform method. The null GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction (PCR) method. The null genotype of GSTM1 and GSTT1 was seen in 45.3% and 40.6% in psoriasis patients whereas in the controls it was 34.4% and 20.0%, respectively. A significant association was seen between the null alleles of the GSTT1 (OR = 2.74) and GSTM1 (OR = 1.58) alone or in combination with tobacco use (P < 0.001) and psoriasis risk. The presence of both null genotypes of GSTM1 and GSTT1 further increased the risk of psoriasis (OR = 3.52) when compared with the positive genotypes of GSTM1 and GSTT1. A major limitation of this study was the small sample size. A large epidemiological study is necessary to confirm these findings. The null genotype of GSTT1 is a strong predisposing factor for psoriasis in North India.

Effects of lymphocyte DNA damage levels in Korean plant food groups and Korean diet regarding to glutathione S-transferase M1 and T1 polymorphisms

Purpose: GST (glutathione S-transferase) M1 and T1 gene polymorphisms are known to affect antioxidant levels. This study was carried out to evaluate genetic susceptibility by measuring the effect of DNA damage reduction in the Korean diet by vegetable food according to GST gene polymorphisms using the ex vivo method with human lymphocytes. Methods: Vegetable foods in the Korean diet based the results of the KNHANES V-2 (2011) were classified into 10 food groups. A total of 84 foods, which constituted more than 1% of the total intake in each food group, were finally designated as a vegetable food in the Korean diet. The Korean diet applied in this study is the standard one-week meals for Koreans (2,000 Kcal/day) suggested by the 2010 Dietary Reference Intakes for Koreans. Ex vivo DNA damage in human lymphocytes was assessed using comet assay. Results: In the Korean food group, the DNA damage protective effect of GSTM1 and GSTT1 was found to be greater in mutant type and wild-type, respectively. and the DNA damage protective effect according to the combined genotype of GSTM1 and GSTT1 was different depending on the food group. On the other hand, in Korean Diet, the DNA damage protective effect appeared to be larger in GSTM1 wild-type than in mutant type and was found to not be affected by GSTT1 genotype. Conclusion: These results can be used as basic data to demonstrate the superiority of the antioxidant function of Korean dietary patterns and food groups. Furthermore, it may be a starting point to begin research on customized antioxidant nutrition according to individual genes.

Is There Any Association between Glutathione S-transferases M1 and Glutathione S-transferases T1 Gene Polymorphisms and Endometrial Cancer Risk? A Meta-analysis.

Epidemiological evidence on the association between genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes and risk of endometrial cancer (EC) has been inconsistent. In this meta-analysis, we seek to investigate the relationship between GSTM1 and GSTT1 polymorphisms and the risk of EC. We searched Medline, PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) for the association were determined using a fixed- or random-effect model. Tests for heterogeneity of the results and sensitivity analyses were performed. A total of six case–control studies were included in the final meta-analysis of GSTM1 (1293 cases and 2211 controls) and GSTT1 (1286 cases and 2200 controls) genotypes. Overall, GSTM1 null genotype was not significantly associated with an increased risk of EC (OR = 1.00, 95% CI = 0.76–1.30, P = 0.982). Similarly, for GSTT1 deletion genotype, we observed no association under the investigated model in the overall analysis (OR = 0.91, 95% CI = 0.64–1.30, P = 0.619). Subgroup analysis also showed no significant association between the GSTM1 null genotype and EC risk in hospital-based design (OR = 1.26, 95% CI = 0.93–1.71, P = 0.131) and no relationship between GSTT1 null genotype with EC risk in population-based design (OR = 1.18, 95% CI = 0.79–1.76, P = 0.407). However, GSTM1 null genotype contributed to an increased EC risk in population-based design (OR = 0.76, 95% CI = 0.60–0.97, P = 0.027), while null GSTT1 in hospital-based studies (OR = 0.70, 95% CI = 0.52–0.93, P = 0.015). The present meta-analysis suggested that GSTs genetic polymorphisms may not be involved in the etiology of EC. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null, and design-specific with the development of EC are needed to prove our findings.

No association between glutathione S-transferase M1 and T1 gene polymorphisms and susceptibility to endometriosis

ABSTRACT Introduction: Endometriosis is a common gynecologic disorder influenced by genetic and environmental factors. The glutathione S-transferase family is associated with endometriosis because its main function is cellular detoxification, so the absence of those enzymes may be a factor for the development of the disorder. Objective: Investigate the relationship between polymorphisms of GSTM1 and GSTT1 genes and endometriosis, in order to gain a better understanding of the association between detoxification genes and the susceptibility to endometriosis. Material and methods: Case-control study in 132 women (49 with endometriosis and 83 of the control group). The genotype was determined using multiplex polymerase chain reaction (PCR), observed in 10% polyacrylamide gel electrophoresis stained with silver nitrate, and statistical analysis was performed. Results: There was not a significant difference between the GSTM1 and GSTT1 null genotype in the endometriosis group and the control group (p = 0.9956). The same result was observed with the combined genotype (p = 0.8129). Conclusion: In the present study, the GSTM1 and GSTT1 polymorphisms are not associated with a higher risk of endometriosis.

Glutathione S-Transferase T1 and M1 Gene Polymorphisms among Breast Cancer Susceptible Ghanaians

Background: Glutathione S-transferase (GST) gene polymorphism has been associated with breast cancer; however, there are conflicting results. Little or no information exists in the Ghanaian population. Aim: To determine the association between GST polymorphic genes (GSTM1 and GSTT1) and susceptibility to breast cancer in Ghanaian population. Method: 112 whole blood samples were retrieved from -80oC freezer. Samples comprised 56 female breast cancer patients. Demographic and clinical data were retrieved from records. Patients were age matched with 56 controls. Genomic DNA was extracted; GSTTI and GSTM1 genes amplified using multiplex PCR with appropriate primers and the resultant amplicons separated by agarose gel electrophoresis. Results: The prevalence of GSTT1 null in patients was 42.9% and with greater association with breast cancer (OR=2.84, 95% CI=1.52–5.29, p=0.001). The heterozygous GSTT1 null/GSTM1 genotype was strongly associated with breast cancer (OR=3.02, 95% CI=1.61–5.66, p 0.05). However, the presence of both genes was not a risk factor of breast cancer in the patients (OR=0.53, 95% CI=0.28–1.09, p=0.030). Conclusion: The GSTT1 null and GSTT1 null / GSTM1 genotypes may be potential risk factors for breast cancer susceptibility.

P.1.a.005 - Glutathione S-transferase M1 gene deletion may be associated with susceptibility to epilepsy

P.1.a.005 - Glutathione S-transferase M1 gene deletion may be associated with susceptibility to epilepsy

Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

BackgroundLung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.Methods and resultsAssessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 ‘CC’ genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 ‘AG’ gene polymorphisms with 8.8-fold risk and GSTT1 (−/−) genotype demonstrated a twofold risk of disease susceptibility.ConclusionsA combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2′-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-016-0209-x) contains supplementary material, which is available to authorized users.

Association of glutathione S-transferases M1, T1 and P1 gene polymorphisms with attention deficit and hyperactivity disorder in Korean children

Attention deficit and hyperactivity disorder (ADHD) is highly heritable disorder and common in school-age children characterized by inattention, hyperactivity and impulsivity. Although its heritability was estimated at 80–90% from family, adoption and twin studies, the molecular etiology of this disorder has not elucidated. Meanwhile, an impaired balance of oxidant-antioxidant status and increased oxidative stress is observed in ADHD, and it may imply a possible relationship between oxidative stress and etiology of ADHD. Glutathione S-transferase (GST) is antioxidant enzymes that play a key role in the cellular detoxification. In the present study, we examined the association between the genetic polymorphisms of GSTM1, GSTP1 and GSTT1, and ADHD in Korean children. Case–control study was conducted with 243 ADHD children and 327 controls. There were no significant associations between the polymorphisms and the incidence of ADHD (p>0.05). However, significant associations were observed in the stratified analyses. The frequency of GSTP1 Ile/Ile genotype is reached to the significant level in the hyperactivity subtype (88.2%) compared to controls (64.8%) (p=0.035) and the frequency of GSTT1-null genotype is significantly higher in the inattentive boys (p=0.005). Similarly, GSTT1-null genotype showed significant associations in combined subtype (p=0.016) and hyperactivity subtype (p=0.036) of the ADHD girls. Thus our result imply that the polymorphisms in the GST genes may affect ADHD, however, replication study for larger sample set and functional studies are crucial to confirm these findings.

Single nucleotide polymorphisms in glutathione S-transferase P1 and M1 genes and overall survival of patients with ovarian serous cystadenocarcinoma treated with chemotherapy.

The effects of platinum-based drugs are controlled by genes that are involved in DNA detoxification, including glutathione S-transferase (GST)P1 and GSTM1, which have been associated with increased benefits in the chemotherapeutic treatment of patients with ovarian cancer. The present study assessed the effect of single nucleotide polymorphisms in GST genes on the overall survival (OS) of patients with ovarian serous cystadenocarcinoma that were treated with chemotherapy. A total of 95 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms in the patients were genotyped using the following methods: Pyrosequencing, to identify GSTP1 Ile105Val; a relative quantification method, to identify the copy number variation in GSTM1; and polymerase chain reaction followed by gel electrophoresis, to identify the null vs. non-null genotypes of GSTM1. The association between genotypes and OS of patients was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The OS of patients treated with paclitaxel + carboplatin-based chemotherapy was significantly increased, compared with patients treated with alternative forms of chemotherapy (P=0.035). The OS of patients did not differ significantly between different GSTP1 genotypes (log-rank test, P=0.17). Cox proportional hazards regression analysis revealed that, since the start of the treatment, there was not a significant association between the GSTP1 isoleucine allele and the OS for heterozygous carriers of the isoleucine allele [hazards ratio (HR), 1.78; 95% confidence interval (CI), 0.77-4.12; P=0.18] and no homozygous carriers of the valine allele had been detected (HR, 0.00). There was no significant difference between GSTM1 genotypes, according to Kaplan-Meier survival analysis (log-rank test, P=0.83). Patients that possessed ≤1 copy of GSTM1 exhibited no decrease in OS (HR, 0.96; 95% CI, 0.37-2.51; P=0.94), compared with patients that possessed two copies of GSTM1 (HR, 0.71; 95% CI, 0.22-2.28; P=0.56). Overall, the present results suggest that there are no associations between polymorphisms in the GSTP1 and GSTM1 genes and the OS of patients with ovarian cancer following administration of adjuvant chemotherapy.

A meta-analysis of association between glutathione S-transferase M1 gene polymorphism and Parkinson's disease susceptibility.

The aim of this meta-analysis was to evaluate whether there was an association between glutathione S-transferase M1(GSTM1)gene polymorphism and Parkinson’s disease (PD) susceptibility by pooling published data.We performed comprehensive electronic database search for articles published between February12,2015 and April30 2016. The published case-control or cohort studies related to GSTM1 gene polymorphism and Parkinson’s disease susceptibility were screened, reviewed, and included in this meta-analysis. The correlation between GSTM1 gene polymorphism and PD susceptibility was expressed by odds ratio (OR) and its corresponding 95% confidence interval (95%CI). Publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test. All analysis was done by stata11.0 software.After searching the PubMed, EMBASE, and CNKI databases, seventeen case-control studies with 3,538 PD and 5,180 controls were included in the final meta-analysis. The data was pooled by a fixed-effect model for lack of statistical heterogeneity across the studies; the results showed GSTM1 null expression can significant increase the susceptibility of PD (OR=1.11, 95% CI:1.01-1.21, P<0.05). Subgroup analysis indicated GSTM1 gene polymorphism was associated with PD susceptibility in the Caucasian ethnic group (OR=1.15, 95% CI:1.05-1.27, P<0.05) but not in the Asian ethnic group (OR=0.89, 95% CI:0.70-1.12, P>0.05). Begg’s funnel plot and Egger’s line regression test showed no significant publication bias.Based on the present evidence, GSTM1 null expression can significant increase the susceptibility of PD in persons of Caucasian ethnicity.

Association of glutathione S-transferases M1 and T1 gene polymorphisms with the risk of metabolic syndrome in an Iranian population.

Background:Glutathione S-transferases (GSTs) are important factors in cell sensitivity to oxidative stress and susceptibility to cardiometabolic disorders. We aimed to investigate the GSTM1 and T1 gene polymorphisms, as well as their interactions in metabolic syndrome (MetS) patients and healthy individuals in an Iranian population.Materials and Methods:The study sample comprised of 220 healthy individuals (mean age: 41.9 – 15.1 years) and 165 MetS patients (mean age: 49.7 – 11.5 years). The diagnostic criteria for MetS were defined following the criteria provided by the modified National Cholesterol Education Program Adult Treatment Panel III. Genotyping of GSTM1 and T1 genes were performed using polymerase chain reaction.Results:Our analyses have shown that neither GSTM1 (odds ratio [OR] =0.89, 95% confidence interval [CI]: 0.59 – 1.33, P = 0.57) nor GSTT1 (OR = 1.26, 95% CI: 0.76 – 2.02, P = 0.38) null genotypes were associated with increased risk. Moreover, no significant differences were observed between various combinations of GST genotypes.Conclusion:Contrary to our primary hypothesis, what we found disaffirms any kind of association between GSTM1 and T1 polymorphisms and the risk of MetS. However, being the first polymorphism study of GSTs in MetS patients, further studies are required to confirm our results in other populations.

Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.

Glutathione S-Transferase M1 and T1 Gene Polymorphisms and the Outcome of Chronic Hepatitis C Virus Infection in Egyptian Patients.

We analysed the distribution of GSTM1 and GSTT1 gene polymorphisms in Egyptian patients with chronic hepatitis C, and investigated their relationship to the clinical outcome of chronic hepatitis C virus (HCV) infection. This study included 169 patients with chronic HCV infection and 145 healthy and matched controls.GSTM1 and GSTT1 polymorphisms were genotyped by multiplex polymerase chain reaction. Individual GSTM1 null and GSTT1 null genotypes were more frequent in patients versus control subjects [OR, 4 (95% CI, 2.5-6.4); P ˂ 0.001] and [OR, 1.7 (95% CI, 1.1-2.6); P = 0.025], respectively. The patient group showed a higher frequency of the combined GSTM1/GSTT1 double-null genotype than the control group [OR, 1.8 (95% CI, 1.1-2.9); P = 0.016]. The distribution frequencies of the combined GSTM1/GSTT1 double-null genotype were significantly different [OR, 0.5 (95% CI, 0.25-0.99); P = 0.049] between F0-F3 and F4. There were no significant differences between the two groups with regard to other genotypes. The combined GSTM1/GSTT1 double-null genotype was significantly increased in Child-Pugh C patients in comparison to Child-Pugh A+B (P = 0.02). There was no significant difference between different classes with regard to other genotypes. In conclusion, we identified an association between the combined GSTM1/GSTT1 double-null genotype and advanced liver fibrosis and outcome of chronic HCV infection in Egyptian patients.

Glutathione S-transferase M1 and T1 gene polymorphisms in Brazilian women with endometriosis.

The glutathione family (GST) genes appear to play a role in the genesis of endometriosis. This case-control study aimed to compare the frequencies of GSTM1 and GSTT1 polymorphisms in women with endometriosis and women without endometriosis. Polymerase chain reaction was performed to analyze the GSTM1 and GSTT1 genotypes among women with surgically and histologically confirmed endometriosis (case group n = 121) and in women without evidence of endometriosis confirmed by laparoscopy for investigation the infertility or for laparoscopic tubal sterilization (control group n = 97). No differences in the frequencies of GSTM1 polymorphism (null genotype) were observed between the cases and controls: odds ratio (OR) = 1.13; 95 % CI 0.656-1.93 (p = 0.659). The GSTT1 polymorphism (null genotype) was more prevalent in the endometriosis group than in the control group (OR = 0.53; 95 % CI 0.94-0.29 (p = 0.039). No relationship between menstrual cycle interval and GSTM1 null genotype frequency was observed in either cases or controls (p = 0.370 and p = 0.664, respectively). In addition, no relationship between menstrual cycle interval and GSTT1 null genotype was observed in cases (p = 0.797) or controls (p = 0.052). GSTM1 null genotype frequency was similar between cases and controls. The GSTT1 null genotype was more frequent in the control group.

Association of CYP1A1 and GSTM1 Polymorphisms With Oral Cancer Susceptibility: A Meta-Analysis.

Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility.The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or fixed-effects model was employed depending on the heterogeneity.In overall analysis, CYP1A1 rs4646903 polymorphism was associated with the risk of oral cancer (CC vs TT: OR 1.65, 95% CI 1.33–2.05; CC vs TC+TT: OR 1.77, 95% CI 1.48–2.11; C vs T: OR 1.17, 95% CI 1.07–1.28), whereas rs1048943 showed no obvious association with oral cancer susceptibility. Moreover, subgroup analysis by ethnicity demonstrated that rs4646903 and rs1048943 both related with increased risk of oral cancer in Asians. Moreover, the analysis based on source of control suggested that rs4646903 could increase the risk for oral cancer in both population- and hospital-based populations, whereas no remarkable relationship of rs1048943 with oral cancer susceptibility was observed. For GSTM1 gene, null genotype appeared to be a risk factor for oral cancer (null vs present: OR 1.23, 95% CI 1.12–1.34), which was also proved in the subgroup analysis.The results demonstrated that CYP1A1 rs4646903 and null genotype of GSTM1 polymorphisms might serve as risk factors for oral cancer.