GSTM1 Gene Polymorphisms Research Articles

A meta-analysis of association between glutathione S-transferase gene polymorphism and osteosarcoma chemosensitivity in Chinese population.

In this study, a meta-analysis was performed to investigate whether there is an association between glutathione S-transferase (GST) gene polymorphism and chemosensitivity in patients with osteosarcoma. A comprehensive electronic database search was performed between January 1, 2016, and May 21, 2016. All eligible studies related to GST gene polymorphism and chemosensitivity in patients with osteosarcoma were screened and included in the current meta-analysis. The association between GSTT1, GSTM1 and osteosarcoma chemosensitivity was demonstrated by odds ratio (OR) and corresponding 95% confidence interval (CI). The publication bias was assessed by Begg's funnel plot. A total of four studies with 681 osteosarcoma patients were included in the present study. The data were pooled by fixed effect model for lack of statistical heterogeneity. The results showed there was no significant association between GSTT1 OR = 1.04, 95% CI: 0.77-1.41, P > 0.05), GSTM1 (OR = 1.08, 95% CI: 0.80-1.46, P > 0.05) gene polymorphism and chemosensitivity in patients with osteosarcoma was found by pooled the published data. Begg's funnel plot indicated no significant publication bias in meta-analysis. Glutathione S-transferase gene polymorphism had no association with chemosensitivity in patients with osteosarcoma.

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.

Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation.

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case-control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene-gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94-1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60-29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.

Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation.

PurposeCisplatin based concomitant chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer (CC). Glutathione S-transferase (GST), a phase II antioxidant enzyme is induced by oxidative stress generated by drugs and reactive oxidants. The present study was undertaken to evaluate the association of GSTM1, T1 and P1 polymorphisms with the outcome of CRT treatment in CC patients.MethodsA total of 227 cervical cancer patients with stages IIB-IIIB treated with the same chemoradiotherapy regimen were enrolled and genotyped for GSTM1, T1 and P1 gene polymorphisms by multiplex polymerase chain reaction (mPCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Overall survival was evaluated using Kaplan-Meier survival function and Cox proportional hazards model. All data were analyzed using SPSS (version 21.0).ResultsStratified analysis showed that GSTM1 null (M1-) genotype was associated with a significantly better survival among patients with stage IIB cervical cancer (log-rank P = 0.004) than cases with stage IIIA/IIIB. Death and recurrence were significantly higher in patients with GSTM1 present genotype (M1+) (P = 0.037 and P = 0.003 respectively) and those with M1- showed reduced hazard of death with an adjusted hazard ratio ‘HR’ of 0.47 (95% CI, 0.269–0.802, P = 0.006). Women with M1- genotype as well as in combination with GSTT1 null (T1-), GSTP1 (AG+GG) and GSTT1 null/GSTP1 (AG+GG) showed better survival and also reduced risk of death (HR = 0.31, P = 0.016; HR = 0.45, P = 0.013; HR = 0.31, P = 0.02 respectively).ConclusionsTo the best of our knowledge, this is the first study to correlate the association of GSTM1, T1 and P1 gene polymorphisms with treatment outcome of CRT treated CC patients. Our results suggested that individuals with GSTM1 null genotype and in combination with GSTT1 null and GSTP1 (AG+GG) had a survival advantage. Such genetic studies may provide prognostic information in CRT treated CC patients.

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.

Organochlorine Pesticides Exposure and Bladder Cancer: Evaluation from a Gene-Environment Perspective in a Hospital-Based Case-Control Study in the Canary Islands (Spain)

ABSTRACTThe incidence of bladder cancer has increased significantly since the 1950s. Pesticide exposure has been linked with increasing bladder cancer incidence, although the evidence is inconclusive. However, most epidemiological studies did not evaluate the potential role played by the organochlorine pesticides, the most widely used pesticides in Western countries from the 1940s to the 1970s. Organochlorine pesticides were banned in the late 1970s because of their persistence in the environment and their carcinogenic and mutagenic effects. Organochlorine pesticides were employed in huge amounts in the Spanish archipelago of the Canary Islands; the authors, therefore, evaluated the role played by organochlorine pesticides exposure on bladder cancer. Serum levels of the most prevalent organochlorine pesticides used in the agriculture of these Islands (dichlorodiphenyltrichloroethane [p,p’-DDT], and its metabolites dichlorodiphenyldichloroethylene [p,p’-DDE] and dichlorodiphenyldichloroethane [p,p’-DDD], hexachlorobenzene, hexachlorocyclohexane isomers, aldrin, dieldrin, endrin, heptachlor, cis-chlordane, trans-chlordane, α- and β-endosulfan, endosulfan sulfate, methoxychlor, and mirex) were measured in 140 bladder cancer cases and 206 controls. GST-M1 and GST-T1 gene polymorphisms were genotyped by polymerase chain reaction (PCR)-based methods. These results showed that serum levels of organochlorine pesticides did not increase bladder cancer risk. On the contrary, total burden of hexachlorocyclohexanes was found to be negatively associated to bladder cancer (odds ratio [OR] = 0.929, 95% confidence interval [CI]: 0.865–0.997; P = .041). This effect disappeared when the distribution of the gluthathione S-transferase polymorphisms was introduced in the statistical model. These results indicate that organochlorine pesticides are not a risk factor for bladder cancer. However, these findings provide additional evidence of gene-environment interactions for organochlorine pesticides and bladder cancer and reinforce the relevance of genes encoding xenobiotic-metabolizing enzymes in bladder cancer.

Prostate cancer and glutathione S-transferase deletions.

GSTM1 and GSTT1 gene polymorphisms have been studied in many populations to evaluate their association with prostate cancer risk with contrasting results. The current study was aimed to find out the association of GSTM1 and GSTT1 gene polymorphisms with prostate cancer in Pakistani men. This case control study included pathologically confirmed prostate cancer patients and age matched male controls. Epidemiological data was collected by a standard questionnaire and presence or absence of GSTM1 and GSTT1 gene was observed by multiplex PCR using CYP1A1 as housekeeping gene. Prostate cancer was more prevalent in age of >60 years and most of the patients were at stage IV (70 %) and have undergone surgery. Family history of cancer, smoking, metastasis and surgery were found to be significant (P<0.05) risk factors in prostate cancer development. Gleason score 7 was most prevalent (40.5 %) in prostate cancer patients. Source of drinking water, residential area, occupation, eating habits and number of family members had no association (P>0.05) with prostate cancer risk. No significant association was found when comparing GSTM1 (OR=0.78) and GSTT1 (OR=0.89) gene deletions with prostate cancer risk. Smoking and TNM staging were also not associated with deletion of GSTM1 and GSTT1 genes. Comparison of dual null deletion of both genes with prostate cancer also showed non-significant associations. Deletion of GSTM1 gene at stage IV prostate cancer patients was significantly higher compared with other stages of cancer while no significance was shown by GSTT1 gene deletion. GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population.

GSTM1 null genotype may be associated with an increased nasopharyngeal cancer risk in South China: an updated meta-analysis and review.

Although many epidemiologic studies investigated the GSTM1 gene polymorphism and its association with nasopharyngeal carcinoma (NPC) in Chinese, definite conclusions cannot be drawn. To assess the impact of of GSTM1 polymorphism on the risk of NPC, an updated meta-analysis was performed in a Chinese population. A total of nine studies including 1,291 cases and 2,135 controls were involved in this meta-analysis. Meta-analysis of those nine studies showed that GSTM1 null genotype was associated with an increased risk of NPC in South China (odds ratio [OR] =1.47, 95% confidence interval [CI]: 1.27–1.70). In subgroup analyses stratified by source of controls, it revealed significant results in population-based studies (OR =1.40, 95% CI: 1.19–1.64). Additionally, a significant association was found in smokers (OR =3.16, 95% CI: 1.76–5.67). This meta-analysis indicated a marked association of GSTM1 with NPC risk in South China, and there might be an interaction between the polymorphism and smoking on NPC. However, further studies with gene–gene and gene–environment interactions are required for definite conclusions.

Glutathione S-Transferase (GST) 유전자 다형성과 항정신병약물로 유발된 하지불안증후군의 연관 연구

Glutathione S-Transferase (GST) 유전자 다형성과 항정신병약물로 유발된 하지불안증후군의 연관 연구

GSTM1, GSTT1 and EPHX1 gene polymorphisms and susceptibility to COPD in a sample of Egyptian population

BackgroundGene polymorphisms and COPD susceptibility have been paid special attention and were explored in a large number of studies. The results varied between studies and populations. We aimed to analyze the relation between susceptibility to COPD and polymorphisms of Glutathione S-transferases (GST); GSTM1, GSTT1 and Microsomal epoxide hydrolase-1 (EPHX1) genes in a sample of Egyptian population. MethodsGenetic polymorphisms of GSTM1, GSTT1 and EPHX1 genes in 146 COPD patients and 130 controls were investigated using multiplex PCR for GSTM1 and GSTT1 genes and PCR-RFLP for EPHX1 genes. ResultsThe frequency of GSTM1-null genotype was higher in patients than in controls (72.6% versus 43.8%, P<0.001). Carriers with both null GSTT1 and GSTM1 genes were at a higher risk of COPD (OR 3.45, 95% CI=1.07–11.14). The frequency of EPHX1 exon 3 His allele was higher in patients than controls (19.2% versus 12.7%, P=0.04). Carriers with exon 3 His allele were at a higher risk of COPD (OR 1.63, 95% CI=1.02–2.6, P=0.04). Carriers with both GSTM1-null and EPHX1 113Tyr/Tyr or EPHX1 113Tyr/His genotypes were at a higher risk of COPD (OR 3.33, 95% CI=1.32–8.35 and OR 14.24, 95% CI=3.02–67.17 respectively). Carriers with both GSTM1-null and EPHX1 139His/His genotypes were at a higher risk of COPD (OR 5.58, 95% CI=2.14–14.52). ConclusionsEPHX1 exon 3 His allele in addition to the coexistence of other genetic variants, were significant risk factors in susceptibility to COPD in the Egyptian population.

Relationship of GSTT1 and GSTM1 Gene Polymorphisms and PAH-DNA Adducts with Pathogenesis of Multiple Myeloma

To explore the relationship of GSTT1, GSTM1 gene polymorphisms and PAH-DNA adduct with pathogenesis of multiple myeloma. The bone marrow samples from 37 newly-diagnosed MM patients and 52 healthy peoples as controls were collected; the PCR-based restriction fragment length polymorphism (PCR-RFLP) method was used to detecte the polymorphism of GSTT1 and GSTM1, and to analysis their relationship with clinical characters of MM patients; the engyme linked immunosorbent assay (ELISA) was performed to detect the concentration of PAH-DNA adducts. GSTT1 null and GSTM1 null genotypes increased the risk of multiple myeloma with OR 2.57 (P=0.035) and 1.37 (P>0.05) respectively. In MM patients group, GSTT1 null genotype in stage III was significantly higher than that in stages I, II (P=0.038). However, no statistically significant association was found between GSTT1 gene polymorphism and clinical characters, such as age, type, hemoglobin, β2-MG, albumin. Compared with Hb≥85 g/L of the newly-diagnosed MM patients, MM patients with Hb<85 g/L had significantly higher incidence of GSTM1 null genetype (P<0.05). The level of PAH-DNA adducts in MM patients was higher than that in controls (2358±1182 pg/ml vs 1853±996 pg/ml) (P<0.05). GSTT1 null genotype with PAH-DNA level≥2100 pg/ml showed a risk index of MM (OR=4.500, P<0.05). GSTT1 gene may have a critical function in the development of MM, and correlates with staging of MM. GSTM1 gene polymorphism correlates with hemoglobin levels of patients with MM. The content of PAH-DNA adducts may play an important role in the pathogenesis of multiple myeloma.

GENOTYPIC TESTING OF FERTILE AGED WOMEN WITH DISORDERS OF VEGETATIVE HOMEOSTASIS AND CHANGES IN REPRODUCTIVE HEALTH

The results of genotypic testing of fertile aged women with disorders of vegetative homeostasis and changes in reproductive health are presented in the article. The frequency of dissemination of deletion GSTM1 gene polymorphism and insertion deletion ACE gene polymorphism in women with such changes in reproductive health as infertility and uterine myoma among Ukrainian population have been investigated for the first time.

Correlation of CYP1A1 and GSTM1 gene polymorphisms and environmental factors to familial aggregation of esophageal cancer among the Kazakh ethnic group in Xinjiang.

This study aimed to investigate the correlation of CYP1A1 and GSTM1 gene polymorphisms and environmental factors to familial aggregation of esophageal cancer (EC) among the Kazakh ethnic group in Xinjiang. CYP1A1 and GSTM1 gene polymorphisms were detected using peripheral blood from 86 subjects belonging to families with EC and 82 control subjects. Additionally, a questionnaire survey was conducted to ascertain environmental risk factors. Combined effects of CYP1A1 and GSTM1 gene polymorphisms and environmental factors in familial aggregation of EC were evaluated. Distribution frequencies of CYP1A1 MspI and GSTM1 genotypes between EC and control families showed significant differences (P = 0.002, P = 0.001). Contribution of interaction between CYP1A1 MspI mutant and GSTM1 deletion polymorphisms to familial aggregation of EC was significant, with OR = 3.571 (95%CI = 1.738-3.346). Logistic multivariate analysis indicated that familial aggregation of EC is correlated with 3 factors: drinking water, intake of fresh vegetables and fruits, and CYP1A1 MspI polymorphism (P = 0.005, P = 0.013, and P = 0.001). Sufficient intake of fresh vegetables and fruits (OR = 0.278, 95%CI = 0.137-0.551) protected against familial aggregation of EC, while drinking water (OR = 3.468, 95%CI = 1.562-6.551) and CYP1A1 MspI polymorphism (OR = 2.732, 95%CI = 1.741-3.886) were the risk factors. In conclusion, CYP1A1 and GSTM1 gene polymorphisms affect familial aggregation of EC among the Kazakh ethnic group in Xinjiang. River water intake and CYP1A1 MspI polymorphism were risk factors that likely contributed to high incidence of EC among families.

Influence of GSTM1, GSTT1, and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Sensorimotor Peripheral Neuropathy Risk.

Background and Aims. Diabetic neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). Genetic susceptibility and oxidative stress may play a role in the appearance of T2DM and diabetic neuropathy. We investigated the relation between polymorphism in genes related to oxidative stress such as GSTM1, GSTT1, and GSTP1 and the presence of T2DM and diabetic neuropathy (DN). Methods. Samples were collected from 84 patients with T2DM (42 patients with DN and 42 patients without DN) and 98 healthy controls and genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. Results. GSTP1 Ile105Val polymorphism was associated with the risk of developing T2DM (p = 0.05) but not with the risk of developing DN in diabetic cases. GSTM1 and GSTT1 gene polymorphisms were associated with neither the risk of developing T2DM nor the risk of DN occurrence in diabetic patients. No association was observed between the patients with T2DM and DSPN (diabetic sensorimotor peripheral neuropathy) and T2DM without DSPN regarding investigated polymorphism. Conclusion. Our data suggest that GSTP1 gene polymorphisms may contribute to the development of T2DM in Romanian population. GSTM1, GSTT1, and GSTP1 gene polymorphisms are not associated with susceptibility of developing diabetic neuropathy in T2DM patients.

Glutathione S-transferase M1 and T1 gene polymorphisms and risk of endometriosis in Tunisian population

Objective: An association between endometriosis and the glutathione S-transferase M1 (GSTM1)- and GSTT1-related genes has been proposed on account of the detoxification properties of the GST enzymes. The aim of the present study was to investigate whether the polymorphisms and null mutations are associated with the susceptibility to endometriosis. Methods: The study included 105 women with endometriosis and 150 healthy women with no laparoscopic evidence of disease. Genotyping of the GSTM1 and GSTT1 gene polymorphisms was performed by Multiplex-PCR. Results: There was a significant association of GSTM1 null and GSTT1 null genotypes with endometriosis both when studied alone (P = 0.001 and P = 0.03, respectively) and in combination (P = 0.00002). Conclusion: The findings suggest that the GSTM1 and GSTT1 gene deficiency predisposes to endometriosis in a Tunisian population and can confer a significant increased risk when the GST null genotypes are combined.

Joint effect of glutathione S-transferase genotypes and cigarette smoking on idiopathic male infertility.

Inconsistent results of association studies investigated the role of glutathione S-transferase genes in idiopathic male infertility may be explained by ethnical differences in gene-gene and gene-environment interactions. In this study, we investigated a joint contribution of GSTM1, GSTT1 and GSTP1 gene polymorphisms and cigarette smoking to the risk of idiopathic infertility in Russian men. DNA samples from 203 infertile and 227 fertile men were genotyped by a multiplex polymerase chain reaction (GSTM1 and GSTT1 deletions) and PCR-restriction fragment length polymorphism (GSTP1 I105V) methods. The GSTP1 genotype 105IV was associated with increased risk of male infertility (OR = 1.50 95% CI 1.02-2.20 P = 0.04). Genotype combinations GSTP1 105II/GSTT1 del (G1), GSTM1 del/GSTT1 del (G2) and GSTM1 + /GSTT1 del (G3) were associated with decreased risk of male infertility (P ≤ 0.003), whereas a genotype combination GSTP1 105IV/GSTT1 + (G4) was associated with increased disease risk (P = 0.001). The genotype combinations G3 and G4 showed a significant association with infertility in smokers; however, nonsmokers carriers did show the disease risk. In conclusion, GSTM1, GSTT1 and GSTP1 genes are collectively involved in the development of idiopathic male infertility and their phenotypic effects on the disease risk are potentiated by cigarette smoking.

Association of DCC, MLH1, GSTT1, GSTM1, and TP53 gene polymorphisms with colorectal cancer in Kazakhstan.

This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR = 3.45, 95% confidence interval (95%CI) = 1.75-6.81, χ (2) = 14.07, p < 0.0002), MLH1 (-93G/G versus G/A and A/A; OR = 1.45, 95%CI = 1.02-2.07, χ (2) = 4.21, p < 0.04), TP53 (Pro72Pro; OR = 3.80, 95%CI = 2.46-5.88, χ (2) = 61.27, p < 0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR = 1.43, 95%CI = 1.00-2.04, χ (2) = 3.90, p < 0.05), and GSTM1 deletions (OR = 1.83, 95%CI = 1.28-2.63, χ (2) = 11.04, p < .001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh-OR = 3.40, 95%CI = 1.63-7.06, χ (2) = 11.35, p < 0.003; for Russian-OR = 4.69, 95%CI = 2.53-8.66, χ (2) = 53.19, p < 0.0001) and GSTM1 deletions (for Kazakh-OR = 2.30, 95%CI = 1.21-4.40, χ (2) = 8.42, p < 0.01; for Russian-OR = 1.64, 95%CI = 1.01-2.66, χ (2) = 7.82, p < 0.02).

Association of GSTM1 and GSTT1 gene polymorphisms and in-vitro fertilisation outcome in a population in northern Iran

Implantation failure is a major limiting step for in-vitro fertilisation (IVF). Embryo implantation is the result of the interaction of the embryo with the endometrium. Oxidative stress (OS) can cause defective embryo development and retardation. Genetic polymorphisms of detoxicating enzymes, such as glutathione S-transferases (GSTs), may play an important role in the outcome of embryo implantation. GSTM1 and GSTT1 are known to be highly polymorphic. The aim of this study was to examine the association of GSTM1 and GSTT1 gene polymorphisms with IVF-ET outcome in a population in northern Iran. Blood samples were collected from 120 infertile women who underwent an IVF cycle, and 108 healthy volunteers. Genomic DNA was prepared from peripheral blood leucocytes. Genotype frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). It was found that 25.8% of the infertile women and 0% of the controls had the GSTM1 null genotype (odds ratio (OR) = 76.37; 95% CI = 4.6–1,265.7; p = 0.0025). On the other hand, 5% of the cases and 0% of the controls had the GSTT1 null genotype (OR = 12.3, 95% CI = 0.68–221/3, p = 0.088). These results suggest that GSTM1 null type might be associated with IVF outcome in a population in northern Iran.

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian pediatric patients with sickle cell disease.

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio = 1.52, 95% confidence interval = 0.42-5.56, P = 0.005). We found no significant association between GST genotypes and frequency of sickle cell-related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Glutathione-S-Transferase M1 and T1 Gene Polymorphisms and Susceptibility to the Progression of Liver Fibrosis in Hcv-Infected Patients in Taiwan

Abstract Background: This study was conducted to evaluate the influence of glutathione-S-transferase (GST) M1 and T1 polymorphisms in 184 patients with different stages of liver fibrosis and hepatitis C virus infection and 173 healthy control subjects. Methods: DNA samples were extracted from whole blood, and the polymorphisms of GSTM1 and GSTT1 were determined with PCR using fluorescence-labeled Taq Man probes. Associations between specific genotypes and progression of liver fibrosis were examined by use of the logistic regression analysis to calculate the odds ratio (OR) and 95% confidence intervals (CI). Results: Results show that no differences were found between the frequencies of GSTM1 (49.8% versus 50.2%) and GSTT1 (52.2% versus 47.8%) null genotypes in HCV-infected pa tients and healthy controls, respectively. In addition, there was also no significant relation between the frequency of GSTM1 or GSTT1 gene polymorphisms and fibrosis stage as classified by the METAVIR group. Conclusions: The combined GSTM1 and GSTT1 null genotypes showed an association between GSTM1 [-]/GSTT1 [- ] and progression of liver fibrosis.