Investigation of glutathione S-transferase M1 and T1 deletions in lung cancer

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions which are responsible for the existence of null genotypes. Previous studies have suggested that GST genotypes may play a role in determining susceptibility to a number of unrelated cancers, including lung cancer. The GSTM1 and GSTT1 polymorphisms were determined by PCR-based analysis in 75 lung cancer patients and 55 controls. The unconditional logistic regression analysis was used to calculate ORs and 95% CI. The frequencies of GSTM1 and GSTT1 null genotypes were 37.3 and 22.7% in lung cancer patients and 27.3 and 16.4% in controls, respectively. When analyzed by histology the GSTM1 null genotype was more prevalent in squamous-cell carcinoma and adenocarcinoma patients. Whereas, GSTT1 null genotype frequency was lower in small-cell lung cancer patients than controls. But these differences were not statistically significant. According to smoking status, null genotype for both gene are associated with an increase in risk for lung cancer. Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related lung cancer.     

Combined genotype analysis of GSTM1 and GSTT1 polymorphisms in a Polish population

This study describes the distribution of GSTT1 and GSTM1 polymorphisms in a normal population of central Poland. A homozygous inherited deletion of either gene leads to absence of enzyme activity in affected individuals, and those lacking more than one detoxifying gene are at the highest risk for diseases caused by environmental factors. The prevalence of the "null" genotype of the GSTM1 and GSTT1 genes was determined by using a multiplex polymerase chain reaction methodology in a group of 233 healthy individuals. We found the following frequencies of individuals with mutated alleles: 47.6% were homozygously deficient for GSTM1 (51.1% males, 42.4% females) and 16.3% for GSTT1 (17.7% males, 15.2% females). The combined analyses GSTM1/GSTT1 revealed the following genotypes: +/+, 44.2% (42.6% males, 46.7% females); "null"/+, 39.1% (39.7% males, 38.0% females); +/"null," 8.6% (7.1% males, 10.9% females); "null"/"null," 8.1% (10.6% males, 4.4% females). Of interest is the small number of women lacking both genes. Significant differences occurred between men and women in some age groups, which could suggest that sex differences in susceptibility to diseases may be caused by genotype differences in detoxifying enzymes such as glutathione S-transferase. The data obtained may prove to be useful for epidemiological studies.     

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population

The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.     

Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study.

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi2=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking and gastric cancer risk

Glutathione S-transferases (GSTs) belong to a superfamily of detoxification enzymes that provide critical defences against a large variety of chemical carcinogens and environmental toxicants. GSTs are present in most epithelial tissues of the human gastrointestinal tract. We investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the interaction with cigarette smoking and susceptibility to gastric cancer. The GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler Instrument. The study included 70 patients with gastric cancer and 204 controls. Associations between specific genotypes and the development of gastric cancer were examined by use of logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 homozygous null genotype was associated with an increased risk of developing gastric cancer (OR = 1.73; 95% CI = 1.10-3.04). GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the risk of gastric cancer. Also there was no difference between cases and controls in the frequency of val-105 and ile-105 alleles (p = 0.07). After grouping according to smoking status, GSTM1 null genotype was associated with an increased gastric cancer risk for smokers (OR = 2.15; 95% CI, 1.02-4.52). There were no significant differences in the distributions of any of the other GST gene combinations. Our findings suggest that the GSTM1 null genotype may be associated with an increased susceptibility to gastric cancer.     

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5% versus 40.3%, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95%CI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country.     

Prevalence of GSTT1, GSTM1 and NQO1 (609C>T) in Filipino children with ALL (acute lymphoblastic leukaemia)

In the present paper, we examined the incidence of polymorphic genes involved with the detoxification of exogenous chemicals, including carcinogens, namely GSTT1 (glutathione transferase theta1), GSTM1 (glutathione transferase mu1) and NQO1 (NAD(P)H:quinone oxidoreductase 1) in 60 Filipino paediatric patients with ALL (acute lymphoblastic leukaemia). We found a significantly high incidence of the GSTM1 null genotype in ALL children (71.7%) compared with 51.7% in the control group of children (P<0.05). The GSTT1 null genotype was observed in 35.0% and 33.3% of the ALL cases and the control subjects respectively, with no significant difference. Screening for NQO1 (609C>T) mutant alleles showed a high incidence of the NQO1 C/C genotype (NQO1 homozygous wild-type allele genotype) in 60.0% of ALL cases and was significantly higher than in the control group (23.3%) (P<0.01). These GSTM1 null and NQO1 wild-type genotypes are independently associated with the risk of ALL in Filipino patients. When these two genotypes, GSTM1 null and NQO1 C/C, were combined, the hazard rate for childhood leukaemia was significantly increased (P<0.001). We also noticed that the incidences of GSTM1 null mutations and the NQO1 C/C genotype were significantly higher among Filipinos. These findings suggest a possible role of the GSTM1 null and NQO1 C/C genotypes in the susceptibility of paediatric ALL cases in the Philippines.     

Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk

The aim of this study was to investigate associations between genetic variability in specific Glutathione S-transferases (GST) genes (GSTM1, GSTT1 and GSTP1) and susceptibility to breast cancer. Genotypes of blood specimen DNA were determined for 65 women with incident cases of breast cancer and 108 control subjects. Associations between specific genotypes and the development of breast cancer were examined by the use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Neither GSTT1 nor GSTM1 homozygous null genotype was associated with a significant increased risk of developing breast cancer. The presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The risk of breast cancer associated with a combined GSTT1 and GSTM1 null genotype was 3.37 (95% CI = 0.76-2.95, p = 0.115). The only significant association between increased risk of breast cancer development and GSTs polymorphisms was found when GSTT1 null, GSTM1 null and the presence of valine in GSTP1 in codon 105 were combined (p < 0.048, OR = 3.75, 95% CI = 1.01-13.90). Our findings suggest that combined genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.     

Null genotype of glutathione S-transferase M1 is associated with senile cataract susceptibility in non-smoker females

In the present study, we investigated whether the polymorphisms of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes are risk factors of cataract among Iranian population in a molecular epidemiological way. Blood samples from 150 subjects with cataract (72 male; 78 female) and 150 age- and sex-matched healthy persons were collected. Both patient and control groups were unrelated Iranian Muslims. Using PCR-based method, the genotypes were determined. The null GSTM1 genotype was associated with a 2.38-fold increase in the risk of developing cataract (OR=2.38; 95% CI=1.46-3.89; P = 0.0003). After stratification by sex of subjects, the association was apparent only among women (OR=3.20; 95% CI=1.58-6.52; P = 0.0007). The GSTT1 null genotype was associated with a 1.10-fold increased risk of developing cataract, but this association was not statistically significant. After stratification by sex of subjects, same results were obtained. Female patients with null genotype for GSTM1 and no history of smoking had a 3.45-fold increased cataract risk (P < 0.05), whereas females who were null for GSTM1 and having history of smoking were not at increased risk of cataract.     

Polymorphisms of the GSTM1 and CYP2D6 genes associated with susceptibility to lung cancer in Chinese.

The case-control study was conducted to examine the association between GSTM1 null and CYP2D6Ch (T(188)/T) genotypes and lung cancer risk among Chinese of Han nationality living in Guangdong. All 191 subjects were investigated with unitary questionnaire and their DNAs were isolated from peripheral lymphocytes by standard procedures with proteinase K digestion and phenol/chloroform extraction. GSTM1(-) was detected with polymerase chain reaction (PCR) in all 191 subjects, involving 59 lung cancer cases, 59 hospital controls and 73 healthy controls. The frequencies of GSTM1(-) were not significantly different between the cases and the two controls overall. However, among adenocarcinoma of lung, the frequency of GSTM1(-) (76.9%) appeared to be higher than that in controls (49.2%), and the odd radios were 3.42-3.45. The results suggested an elevated risk for adenocarcinoma of lung would be shown by GSTM1(-). Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) to detect CYP2D6 T(188)/T genotype in 59 lung cancer patients and 59 hospital controls, it showed no significant difference between the two groups. However, non-smokers with non-T(188)/T (C(188)/C or C(188)/T) genotype showed 3.78-folds increased risk of lung cancer compared with those with T(188)/T genotype (P=0.036). The data did not suggest a substantial interaction effect between GSTM1 and CYP2D6 polymorphisms and the risk of lung cancer. Additionally, among Chinese (Han) of Guangdong, the frequency of CYP2D6 T(188) allele appeared to be 57.2%, and GSTM1(-) to be 51.8%.     

Glutathione S-transferase M1, T1, and P1 genotypes and breast cancer risk: a study in a Portuguese population

Glutathione S-transferases are a superfamily of multifunctional enzymes that play a key role in Phase II metabolism, detoxifying therapeutic drugs, and various carcinogens by conjugation with glutathione. We undertook a case-control study in Central-Eastern Portuguese population to evaluate the association of null genotype in GSTM1 and GSTT1 along with the polymorphism in GSTP1 (A/G) and susceptibility to breast cancer. The population sample consisted of 85 patients with histological diagnosis of breast cancer and 102 healthy women. Genomic DNA was extracted from blood samples, and genotyping analyses were performed by PCR-based methods. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. We found a increased breast cancer risk associated with GSTM1 null genotype (OR = 3.597; 95% CI = 1.849-6.999; P = 0.0001) and GSTT1 (OR = 2.592; 95% CI = 1.432-4.690; P = 0.002), but the presence of valine alleles compared to isoleucine alleles in codon 105 in GSTP1 did not increase the risk of breast cancer development. The two-way combination of GSTM1 and GTTT1 null genotypes resulted in 8-fold increase for breast cancer risk (OR = 8.287; 95% CI = 3.124-21.980; P = 0.0001) and the three-way combination of GSTP1 105AA/AG and null genotypes for both GSTM1 and GSTT1 resulted in 5-fold increase for breast cancer risk (OR = 5.040; 95% CI = 1.392-18.248; P = 0.016). Our results suggest that GSTM1 and GSTT1 null genotype alone, both combined or combined with GSTP1 valine alleles, are associated with higher susceptibility to breast cancer development.     

Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence

Research has shown that genetic polymorphisms in biotransformation enzymes, such as CYP1A1 and GSTM1, are related to a greater or lesser susceptibility to various cancers. We made an analysis of CYP1A1m1 SNP and GSTM1 null genotypes in a family group (71 members) related by consanguinity who had an unusually high incidence of cancer and a high frequency of smokers. There were no significant differences in genotype frequencies in this family when compared to data for Brazilian populations. Possibly, the high incidence of cancer in this sample is associated with smoking and/or other factors not detected in this survey.     

Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) in selected populations of Afghanistan

Genetic polymorphisms in genes encoding glutathione S-transferase T1 (GSTT1, a member of class theta) and M1 (GSTM1, a member of class mu) have been defined. Previous studies have revealed that there was significant difference between populations for allelic frequency of several members of GSTs. In order to find the prevalence of null genotypes of GSTM1 and GSTT1 in Afghanis populations the present study was carried out. The total study subjects consisted of 656 unrelated healthy Afghanis refugees living in Fars province (southern Iran). From these 257, 217, 120, and 62 individuals were Pashtuns, Tajiks, Hazaras, and Uzbeks, respectively. Genetic polymorphisms for GSTT1 and GSTM1 were detected by multiplex PCR. The prevalence of null genotype of GSTM1 in Pashtuns, Tajiks, Hazaras, and Uzbeks was 42.4, 48.4, 52.5, and 40.3 %, respectively. There was no significant difference between these populations for the genotypic distribution of the GSTM1 polymorphism (χ(2) = 4.67, df = 3, P = 0.197). The frequency of GSTT1 null genotype in Pashtuns, Tajiks, Hazaras, and Uzbeks was 7.4, 25.3, 25.0, and 29.0 %, respectively. The observed difference between populations for prevalence of GSTT1 null genotype was statistically significant (χ(2) = 35.54, df = 3, P < 0.001). In comparison with European and Asian populations, Afghanistan populations like Iranian populations showed intermediate frequency for GSTT1 and GSTM1 null genotypes.     

The association between GSTM1 polymorphism and gastric cancer risk: a meta-analysis

Relationship of gastric cancer with the GSTM1 polymorphism was reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between GSTM1 polymorphism and gastric cancer susceptibility. Relevant studies were identified from PubMed and references of retrieved articles. A meta-analysis was performed, which included 38 studies with 6,605 gastric cancer cases and 11,311 controls. The combined result based on all studies showed there was a significant link between GSTM1 null genotype and gastric cancer (OR = 1.20, 95%CI: 1.08–1.34). When stratifying for the race, the phenomenon was found that gastric cancer case had a significantly higher frequency of GSTM1 null genotype than control in Asians (OR = 1.27, 95%CI: 1.10–1.47). However, there was not enough evidence to show there was a significant difference in GSTM1 null genotype distribution between gastric cancer case and control in Caucasians (OR = 1.13, 95%CI: 0.96–1.32). This meta-analysis indicated that GSTM1 null genotype might be associated with increased gastric cancer risk in Asians. However, this meta-analysis did not provide an evidence of confirming association between GSTM1 polymorphism and gastric cancer in Caucasians.     

The role of human glutathione S-transferases M1 and T1 in individual susceptibility to bladder cancer

Several genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. This study is focused on the polymorphic enzymes glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) that are involved in the detoxification of many xenobiotics involved in the etiology of bladder cancer. To investigate the role of GSTM1 and GSTT1 in bladder carcinogenesis, the polymerase chain reaction was used to determine GSTM1 and GSTT1 genotypes of cancer patients (n = 76) and controls (n = 248). The proportion of putative risk GSTM1 null genotype in the case group was 52.6%, compared to 49.6% in the control group, but the GSTT1 0/0 frequency in the bladder cancer group was significantly higher (P = 0.04) in comparison with the control group (27.6 vs 16.9%). Individuals lacking the GSTT1 gene are at an approximately 1.9-fold higher risk (OR = 1.87, C.I. 95% = 1.03-3.42) of developing bladder cancer in comparison with individuals with at least one active allele in the GSTT1 locus. A significantly higher incidence of GSTM1 deletion genotype (P = 0.02) was found in smokers with bladder cancer compared to the controls (70.6 vs 49.6%). Smokers lacking the GSTM1 gene are at an approximately 2.4-fold higher risk of bladder cancer (OR = 2.44, C.I. 95% = 1.10-5.30). The effect of smoking associated with the GSTT1 0/0 genotype was not found to affect the risk of bladder cancer.     

The GSTM1 Null Genotype Increased Risk of Gastric Cancer: A Meta-Analysis Based on 46 Studies

Background

Glutathione S-transferases M1 (GSTM1) is an important phase II metabolizing enzyme. The null genotype of GSTM1 causes total loss of GSTM1 enzyme activity and numerous studies have investigated the association between GSTM1 null genotype and gastric cancer risk.

Methods

This meta-analysis was designed to investigate the relationship between GSTM1 null genotype and susceptibility to gastric cancer and assess the influence of Helicobacter pylori infection, smoking, Lauren’s classification, and other factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength.

Results

A total of 46 eligible studies were indentified and analyzed in this meta-analysis, including 8138 cases of gastric cancer and 13867 controls. Pooled results showed that the GSTM1 null genotype was associated with a significantly increased risk of gastric cancer (OR=1.217, 95% CI: 1.113-1.331, P_{heterogeneity}<0.001). Sub-group analysis suggested that the significant association was only observed in Asians (OR=1.273, 95%: 1.137-1.426, P_{heterogeneity} = 0.002), but not in Caucasians. The increased risk was found among H. pylori positive population (OR=1.928, 95% CI: 1.028-3.615, P_{heterogeneity}=0.065), while no association was found among H. pylori negative population (OR=0.969, 95% CI: 0.618-1.521, P_{heterogeneity}=0.168). For smoking status, the GSTM1 null genotype increased risk of gastric cancer in both ever-smokers and non-smokers. Source of control, sample size, location of tumor and Lauren’s classification did not modify the association.

Conclusions

In this meta-analysis based on 46 epidemiological studies, we show that the GSTM1 null genotype is associated with an increased risk of gastric cancer among Asians but not among Caucasians. H. pylori infection but not smoking status could modify the association.     

Interaction between smoking,GSTM1 deletion and colorectal cancer: results from the GSEC study

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-μ (GST-μ). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-μ enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (χ²=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Trimodal GSTT1 and GSTM1 genotyping assay by real-time PCR

The GSTT1 and GSTM1 genes are characterized by the existence of a GST*0 null allele responsible for a lack of enzyme activity, with the respective null genotypes GSTT1*0/0 and GSTM1*0/0. The three resulting genotypes (GSTs*1/1, *1/0 and *0/0) are associated with a trimodal distribution of glutathione-conjugator activity. Previous epidemiological studies have only evaluated the cancer risk associated with the GST null genotype relative to the two GST carrier genotypes (GSTs1*1/1 and *1/0). We developed GSTT1 and GSTM1 TaqMan real-time quantitative PCR assays to discriminate each of the three genotypes, with the albumin gene (ALB) as reference. The mean N(GSTT1*1/1) value was 1.0 (95% confidence interval 0.80-1.20). The mean N(GSTT1*1/0) value was 0.48 (95% CI 0.36-0.60). One (3.4%) of the 29 DNA samples yielded the GSTM1*1/1 genotype (N(GSTM1*1/1) = 1), a frequency in keeping with the Hardy-Weinberg distribution. The mean N(GSTM1*1/0) value was 0.50 (95% CI 0.42-0.58). All GSTT1*0/0 and GSTM1*0/0 samples yielded N(GST) values of 0 (Ct = 40); the frequencies of these genotypes (27.6% and 55.2%, respectively) were in keeping with published data. The GSTT1 and GSTM1 real-time PCR assays described here unambiguously discriminate each of the three existing genotypes which should be valuable for assessing the relative risk of cancer associated with each of the three GST genotypes.     

The glutathione S-transferase M1 and P1 polymorphisms and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the Glutathione S-transferase M1 (GSTM1) and P1 (GSTP1) polymorphisms confer susceptibility to rheumatoid arthritis (RA). Meta-analysis was performed on the associations between the GSTM1 and GSTP1 null genotypes and RA, and on the association between smoking or seropositive status and the GSTM1 null genotype in RA patients. Twelve studies involving 3,990 RA patients and 2,815 controls were included in the meta-analysis. All 12 studies examined the GSTM1 polymorphism and three the GSTP1 polymorphism. Meta-analysis of GSTM1 null polymorphism in 2,291 RA and 2,713 control subjects revealed no association between RA and the GSTM1 null genotype (OR?=?1.139, 95?% CI?=?0.914–1.419, p?=?0.246). Stratification by ethnicity indicated no association between the GSTM1 null genotype and RA in Asians or Europeans (OR?=?1.245, 95?% CI?=?0.729–2.124, p?=?0.422; OR?=?1.023, 95?% CI?=?0.794–1.318, p?=?0.863). Furthermore, there was no association between smoking and the GSTM1 null genotype (OR?=?0.943, 95?% CI?=?0.734–1.210, p?=?0.642). In addition, no association was found between seropositive status including anti-CCP (anti-citrullinated antibody) and/or RF (rheumatoid factor) and the GSTM1 null genotype. Meta-analysis of 915 RA and 1,082 controls revealed no association between RA and the GSTP1 null genotype (OR?=?0.965, 95?% CI?=?0.802–1.161, p?=?0.704). Furthermore, stratification by ethnicity indicated no association between the GSTP1 null genotype and RA in Europeans (OR?=?0.794, 95?% CI?=?0.594–1.061, p?=?0.119). This meta-analysis suggests that the GSTM1 and GSTP1 polymorphisms are not associated with the risk of RA. However, due to the small number of studies included and our inability to perform subgroup analysis by environmental factors, further studies are required to explore the roles played by GSTM1 and GSTP1 polymorphisms in the pathogenesis of RA.     

Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes

Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case–control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14–2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37–2.64, P < 0.001), but was not associated with risk of type 1 diabetes (OR = 0.84, 95 % CI 0.66–1.07, P = 0.153). Subgroup analysis by ethnicity further identified the obvious association between GSTM1 null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.