GSTM1) And T1 Research Articles

Glutathione S-Transferase Gene Polymorphisms as Predictors of Methotrexate Efficacy in Juvenile Idiopathic Arthritis.

Because of the unpredictable efficacy of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA), the possibility of a favourable outcome is reduced in more than 30% of patients. To investigate the possible influence of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene deletion polymorphisms on MTX efficacy in patients with JIA, we determined these polymorphisms in 63 patients with JIA who did not achieve remission and 46 patients with JIA who achieved remission during MTX therapy. No significant differences were observed in the distribution of single GSTM1 or GSTT1 deletion polymorphisms or their combination between the two groups: 58.7% to 63.5%; p = 0.567, 17.4% to 22.2%; p = 0.502, and 13% to 12.7%; p = 0.966, respectively. Our results suggest that GSTM1 and GSTT1 deletion polymorphisms do not influence the efficacy of MTX in patients with JIA. Additional studies are required to determine the possible influence of GST deletion polymorphisms on MTX efficacy in patients with JIA.

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia.

Polymorphisms in glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) can cause an entire gene deletion. The current methodology can accurately identify GSTM1 and GSTT1 copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of GSTM1 and GSTT1 and their relationship to the risk of liver cirrhosis. In this study, we compared 106 patients with liver cirrhosis to 104 healthycontrols. Real-time PCR was used to identify the CNVs of GSTM1 and GSTT1. Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively. In 3.3% of the study participants, >2 copies of the GSTM1 or GSTT1 genes were detected. GSTT1 carriers had a significantly lower risk of liver cirrhosis (p<0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant (p<0.05) in patients with a single copy of the GSTT1 gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥2 copies of combined GSTM1 and GSTT1 also had a significantly (p<0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, p trend <0.001). Moreover, ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively. A single copy number of GSTT1, and ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene-environment interactions in the multifactorial development of liver cirrhosis.

Role of Glutathione-S-Transferase M1 (GSTM1) and T1 (GSTT1) Genes on Aluminum Concentration and Oxidative Markers among Autistic Children

Autism Spectrum Disorder (ASD) is considered a multifaceted neurodevelopmental disorder. The last two decades showed an increase in its prevalence until reached about 1 in 54 children. Autistic symptoms may be exacerbated when the interaction of the genetic and the environmental risk factors occur, suggesting that gene-environment interaction could be a mechanism underlying the etiology of ASD. Aluminum is a known neurotoxic metal that has known health effects in humans. Glutathione-S-transferase (GST) genes and their enzymes play a major role in the detoxification of many toxic metals.Data were collected from 76 children aged 2-8 years diagnosed with ASD and 30 sex and age matched healthy children. The aim of this study was to investigate the association of polymorphisms in the two GST genes (GSTM1 and GSTT1) with mean aluminum concentrations (as, gene-environment interaction) and oxidative status markers (GST enzyme, malondialdehyde and nitric oxide) among the studied groups. The study started at December 2019 and last for one year at the clinics of National Research Centre, Egypt.The results of this study showed that the null GSTM1 and GSTT1 genotype is the most common type in ASD and that genotype may predispose ASD children to decreased antioxidant status (GST enzyme activity) which in term lead to mal detoxification of aluminum. There is marked increase in aluminum concentrations in hair of ASD children and oxidative markers (increase in MDA and NO) leading to oxidative damage that may play an important role in children autistic status. The study recommends adding antioxidant supplements to daily diet of ASD children to improve their antioxidant status and in term improving management of patients with autism spectrum disorders. Further studies are needed to describe other GST gene polymorphisms.

Evaluation of associations of GSTM1/GSTT1 null genotypes with the susceptibility to age-related macular degeneration: A meta-analysis

Background: The relationship between glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null genotypes (homozygotes for the null alleles) and the susceptibility to age-related macular degeneration (ARMD) have been reported and revealed inconsistent results. Therefore, the current meta-analysis was carried out. Methods: Eligible published articles (before December 2020) were found by searching 8 databases. The data was extracted from articles. The heterogeneity across studies was estimated using Q and I 2 statistics and the odds ratios (ORs) and its 95 % confidence intervals (95 % CI) were estimated. Results: In total, 6 independent studies including 1089 participants (634 controls and 455 patients) were used in the current study. There was no heterogeneity between studies for both polymorphisms. Statistical analysis showed that the null genotypes of the GSTM1 (OR = 1.18, 95 % CI: 0.91 - 1.53, p = 0.191) and GSTT1 (OR = 0.84, 95 % CI: 0.60 - 1.18, p = 0.328) loci were not correlated with the susceptibility to ARMD. Conclusion: The GSTT1 and GSTM1 genetic polymorphisms did not associated with the risk of ARMD in Caucasian populations.

Additive effect of glutathione S-transferase T1 active genotype and infection with Toxoplasma gondii for increasing the risk of schizophrenia

Purpose To determine if Toxoplasma gondii (T. gondii) infection may play a role in the development of schizophrenia in genetically susceptible persons with regard to genes encoding glutathione S-transferase T1 (GSTT1) and M1 (GSTM1). Methods A total of 78 cases with psychiatric diagnosis of schizophrenia were compared with 91 healthy controls. For detection of IgG antibodies, enzyme-linked immunosorbent assay was used. Genotyping of GSTM1 and GSTT1 was performed by multiplex PCR. Chi-square and logistic regression were used for statistical analyses. Results A higher frequency of the GSTT1 active gene in schizophrenic patients was observed. When risk categories based on the combination of T. gondii status and GSTs polymorphisms were compared, risk of schizophrenia increased in T. gondii positive/GSTT1 absent subjects (OR = 4.75, p = 0.05) compared with T. gondii negative/GSTT1 absent group. When T. gondii positive subjects had the GSTT1 active genotype, the risk increased linearly (OR = 10.20, p < 0.001). Odds ratio in T. gondii positive groups were almost the same in combination with the GSTM1 active genotype (OR = 4.45, p = 0.003) or null genotype (OR = 4.37, p = 0.006). Conclusions Our results showed an additive effect for T. gondii and GSTT1 active genotype as risk factors for schizophrenia in Iranian population. This is a small pilot study and replicating the study with larger groups of patients in multinational investigation to clarify these findings is recommended.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso.

Background and objective Breast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer. Methods Genomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI). Results No correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45). Conclusion Our results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.

Abstract 623: Iron intake, oxidative stress-related genes, and breast cancer risk

Abstract Background: Iron has been shown to enhance breast carcinogenesis in animal models through generation of oxidative stress, although epidemiological evidence of the association between iron intake and breast cancer risk remains inconclusive. This study investigated associations between different types of iron intake and breast cancer risk, and whether these associations were modified by genetic polymorphisms in antioxidant enzymes, including manganese superoxide dismutase (MnSOD) and glutathione S-transferases M1 (GSTM1) and T1 (GSTT1). Methods: A population-based case-control study in Ontario, Canada recruited 3,030 breast cancer cases identified from the Ontario Cancer Registry and 3,402 controls from random digit dialing. Iron intake from foods and supplements was assessed using a 178-item food frequency questionnaire. Multivariable logistic regression analyses were used to evaluate associations between breast cancer risk and intakes of dietary, supplemental, and total (dietary plus supplemental) iron, among all women and stratified by menopausal status. Associations were also examined by hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)] tumor subtype. Among women providing saliva (DNA) samples (1,696 cases and 1,761 controls), interactions between iron intake and genetic polymorphisms were assessed using the likelihood ratio test. Results: Among all women, intakes of dietary, supplemental, and total iron were not associated with breast cancer risk, overall or by tumor subtype. Among premenopausal women, there was an increase in breast cancer risk for the ER–PR– subtype associated with higher intakes (highest vs. lowest quintile) of dietary [odds ratio (OR) = 1.4; 95% confidence interval (CI): 0.9–2.4] and total (OR = 1.8; 95% CI: 1.1–2.9) iron (P for trend &amp;lt; 0.05). Among postmenopausal women, supplemental iron intake (&amp;gt;18 vs. 0 mg/day) was associated with reduced breast cancer risk (OR = 0.7; 95% CI: 0.5–0.9), with similar associations across tumor subtypes. Associations of dietary and total iron intake with overall breast cancer risk were modified by GSTT1 and/or GSTM1/T1 combined genotypes (P for interaction &amp;lt; 0.05). For example, among women with deletions in both GSTM1 and GSTT1 loci, higher dietary iron intake was associated with increased breast cancer risk (OR = 2.1; 95% CI: 1.1–4.2), whereas null or inverse associations were found among women with other GSTM1/T1 genotypes. Conclusions: Results from this study suggest that higher dietary and total iron intake may be associated with increased risk of ER–PR– breast cancer among premenopausal women, whereas higher supplemental iron intake may be associated with reduced postmenopausal breast cancer risk. In addition, associations between iron intake and breast cancer risk may be modified by polymorphisms in oxidative stress-related genes. Our ongoing work will investigate heme and non-heme iron intake in relation to breast cancer risk. Citation Format: Vicky C. Chang, Michelle Cotterchio, Susan J. Bondy, Joanne Kotsopoulos. Iron intake, oxidative stress-related genes, and breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 623.

Prevalence of glutathione s-transferase genes some polymorphisms in menopausal women of two ethnic groups with insomnia

Introduction: According to the current data, most menopausal women have reduced quality of life and one of the main criteria of it is sleep disturbances. It is highly possible, that main consequences of sleep loss may be oxidative stress. Glutathione system is the one of the important components of the antioxidant defense system, which includes glutathione and enzymes. It has been shown that the activity of these enzymes is determined by the polymorphic variants of the corresponding genes. The aim of this research is to carry out a comparative analysis of the frequency distribution of Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes in Caucasian and Asian menopausal women with insomnia.

Glutathione S-transferase M1 and T1 polymorphisms and the risk of mild hepatotoxicity induced by carbamazepine in a tunisian population study

BackgroundThe aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity.MethodsA cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods.ResultsOur results showed that the frequencies of GSTM1 (−) null allele and GSTT1 null (−) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (−) allele than in GSTM1 (+) (p = 10−3.and 0.004, respectively).The level of ALT was significantly higher in combination of GSTM1 (−)/T1(−) than in combined GSTM1(−)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(−)/T1(−) and in combination of GSTM1(+)/T1(−) than in combination of GSTM1(+)/T1(+) (p = 10−3 and 10−3, respectively).ConclusionsOur findings suggest that the GSTM1 (−) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (−) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms and Lung Cancer Risk among a Select Group of Iranian People

Objective(s):Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughout the world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related to the antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people.Materials and Methods:One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, were recruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues of the select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 were investigated by multiplex polymerase chain reaction.Results:With the 240 samples studied, no specific relationship with lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1 (P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, taking into account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was different from that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1 genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk of developing LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52).Conclusion:Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranian people. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.

Association of glutathione S-transferase M1 and T1 polymorphisms and temperament.

Mizaj (Temperament) is one of the basic concepts of Iranian Traditional Medicine (ITM), which has great importance in diagnosis and treatment of diseases, as well as maintaining the ideal healthy state of an individual. However, very little is known about the biological mechanisms of mizaj dependence treatment in practical ITM. This study was aimed to evaluate any association between the mizaj and glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in healthy people. The samples included 247 healthy males from Fars province, southern Iran. The mizaj was determined using a self-reported mizaj identification scale. Subjects with equilibrium or any of four simple mizajes (warm, cold, moist, and dry) were included in the study. The GSTM1 and GSTT1 genotypes were determined using a polymerase chain reaction (PCR)-based method. No any differences in the frequency of GSTM1/T1 polymorphism between equilibrium and each of other mizaj groups were found. However, when equilibrium, moist, and dry groups were pooled and as a "medium warmness" group were compared to the warm group, the frequency of GSTT1-null in the warm group was significantly higher compare to that in the medium warmness group. Also, the combination genotypes of GSTM1 and GSTT1 was associated with the warmness; that is, individuals with combination of GSTM1 positive and GSTT1 null were more susceptible to have a warm temperament. This study indicated that the mizaj could be affected by GSTM1/T1 genes, although further research with larger samples is needed to reach full conclusions.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany

ABSTRACTThis study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

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.

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 between Dietary Patterns and Atopic Dermatitis in Relation to GSTM1 and GSTT1 Polymorphisms in Young Children.

Previous research suggests the association of glutathione S-transferase (GST) gene polymorphisms or diet, but no interactions between these factors in atopic dermatitis (AD). We conducted a community-based case-control study including 194 AD and 244 matched non-AD preschoolers. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) present/null genotypes were evaluated uisng a multiplex PCR method. We measured dietary intakes by a validated food frequency questionnaire and constructed three dietary patterns such as “traditional healthy”, “animal foods”, and “sweets” diets. In stratified analyses by GST genotypes, the “traditional healthy” diet and reduced AD showed association only in the GSTM1-present group (odd ratio (OR) 0.31, 95% confidence interval (CI) 0.13–0.75). A similar pattern of the association existed in the combined GSTM1/T1 genotype that indicated the inverse association between the “traditional healthy” diet and AD in the double GSTM1/T1-present genotype group (OR 0.24, 95% CI 0.06–0.93). Results from the multiplicative test analyses showed that the “traditional healthy” diet on reduced AD was significant or borderline significant in the GSTM1-present group (OR 0.71, 95% CI 0.54–0.92 vs. GSTM1-null group) or the GSTM1/T1 double present group (OR 0.63, 95% CI 0.39–1.03 vs. GSTM1/T1 double null group). These findings demonstrate that the present type of GSTM1 may increase susceptibility to the potential effect of the “traditional healthy” diet on AD.

Association of Functional Polymorphisms in Matrix Metalloproteinase-9 and Glutathione S-Transferase T1 Genes with Temporomandibular Disorders.

To investigate the potential role of polymorphisms in matrix metalloproteinase-9 (MMP-9), glutathione S-transferase M1 (GSTM1) and T1 (GSTT1), and methylenetetrahydrofolate reductase (MTHFR) genes as risk factors for development of temporomandibular disorders (TMD) in a Serbian population. This case-control study included 282 subjects: 100 with TMD and 182 healthy controls. Genotyping was done by means of polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) for single nucleotide polymorphisms (SNPs) analysis (C-1562T MMP-9 and C677T MTHFR) or multiplex PCR and real-time PCR methods for deletion analysis (GSTM1, GSTT1) of DNA obtained from buccal swabs. The association of gene variants with TMD risk was determined by calculating odds ratios (OR) and their 95% confidence intervals (CI). A statistically significant difference in genotype and allele frequencies was found between the TMD group and controls for the MMP-9 SNP. Heterozygotes (CT) were significantly more frequent in the TMD group than in the control group and carriers of the T allele had an approximately twofold increase of TMD risk (OR = 2.13, 95% CI = 1.24-3.67, P = .005). The null GSTT1 genotype as well as the combined non-null GSTM1/ null GSTT1 were associated with lower risk of TMD (OR = 0.28, CI = 0.10-0.74, P = .004 and OR = 0.16, CI = 0.03-0.58, P < .001, respectively). GSTM1 alone and MTHFR polymorphisms did not show an association with TMD. The C-1562T SNP in the promoter region of the MMP-9 gene, the GSTT1 null, as well as the combined GSTM1 non-null and GSTT1 null genotypes are modulators of TMD risk in a Serbian population.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis.

BackgroundSome studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent.ObjectiveIn order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension.MethodsEligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models.ResultsRegarding the GSTM1 null/present genotype, 14 case—control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case—control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected.ConclusionThis meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.

Metabolic gene variants associated with chromosomal aberrations in healthy humans.

Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome-type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid-type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown. Here, we want to test whether variants in metabolic genes associate with CAs in healthy volunteers. Cases were considered those whose total CA (CAtot) frequency was >2% and for CSA and CTA the limit was >1%. Controls had lower frequencies of CAs. Functional polymorphisms in seven genes were selected for analysis: cytochrome P450 1B1 (CYP1B1), epoxide hydrolase 1 (EPHX1), NAD(P)H:quinone oxidoreductase 1 (NQO1), each coding for phase 1 enzymes, and glutathione S-transferase P1 (GSTP1), glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), coding for enzymes which conjugate reactive metabolites, that is, phase 2 enzymes. The number of volunteers genotyped for each gene varied from 550 to 1,500. Only EPHX1 was individually associated with CAtot; high activity genotypes decreased CAtot. A total of six significant (P < 0.01) pair-wise interactions were observed, most including a GST variant as one of the pair. In all genotype combinations with significant odds ratios for CAs a GST variant was involved. The present data provide evidence that variants in genes coding for metabolic enzymes, which individually have small effects, interact and are associated with CA frequencies in peripheral lymphocytes of healthy volunteers.

An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1 and GSTT1) Polymorphisms to Age-Related Cataract.

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.

Role of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) genes in the development and progress of chronic myeloid leukemia and in the formation of response to imatinib therapy.

The effects of GSTM1 and GSTT1 gene deletion ("zero") polymorphisms on the risk of chronic myeloid leukemia development and progress and on response to imatinib monotherapy were studied in the representatives of the Russian nationality in the Vyatka region of Russia. Homozygotic carriership of GSTT1 "zero" allele was associated with a 3.66 times higher risk of chronic myeloid leukemia development in residents of the Vyatka region (OR=3.66, 95% CI=2.12-6.30; p<0.0001). Combinations of the "zero" GSTM1 and GSTT1 genotypes were risk factors indicating the probable disease progress and failure of high cytogenetic response after 12 months of imatinib therapy (400 mg daily).