An evidence for correlation between the glutathione S-transferase T1 (GSTT1) polymorphism and outcome of COVID-19.
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ABSTRACT:
SUBMITTER: Saadat M
PROVIDER: S-EPMC7245315 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
An evidence for correlation between the glutathione S-transferase T1 (GSTT1) polymorphism and outcome of COVID-19.
Clinica chimica acta; international journal of clinical chemistry 20200523
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Project description:BackgroundPrevious studies have revealed significant differences between populations for genotypic frequencies of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms. In order to find the frequency of the null genotypes of GSTM1 and GSTT1 in Iranian populations, the present study was carried out.MethodsThe total study subjects consisted of 1340 unrelated healthy Muslims/Iranian. From these 297, 200, 123, 168, 152, 200, and 200 individuals from Tabriz (East Azerbaijan Province; belong to Azaris), Yasuj (Kohgiluyeh-va-Boyerahmad Province; belong to Lurs), Abarku (Yazd Province; belong to Persians), Zahedan (Sistan-va-Balouchestan Province; belong to Balouchis), Zahedan (Sistan-va-Balouchestan Province; belong to Sistanis), Kermanshah (Kermanshah Province; belong to Kurds), and Gorgan (Golestan Province; belong to Turkmen) respectively. The genotypes were detected by multiplex PCR.ResultsThe frequency of GSTM1 null genotype among Azaris, Lurs, Persians, Balouchis, Sistanis, Kurds, and Turkmen was 43.8, 50.0, 52.0, 50.0, 51.3, 56.0, and 53.0%, respectively. There was no significant difference between these populations for the genotypic distribution of the GSTM1 polymorphism (χ(2)=8.47, df=6, P=0.206). The frequency of GSTT1 null genotype among Azaris, Lurs, Persians, Balouchis, Sistanis, Kurds, and Turkmen was 18.2, 17.0, 29.3, 20.8, 17.8, 18.5, and 23.0%, respectively. There was very similarity between Azaris, Kurds and Lurs for the frequency of GSTT1 genotypes (χ(2)=0.17, df=2, P=0.916).ConclusionBy comparing the frequency of GSTT1 genotypes among Iranian populations, Caucasians and Asians, it is concluded that Azaris, Kurds and Lurs were similar to each other. Taken together, it is suggested that although Azaris are Turkish speaking belong to Caucasians.
| S-EPMC4724738 | biostudies-literature
Project description: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.
| S-EPMC4351109 | biostudies-literature
Project description:Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTT1-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.
| S-EPMC3735287 | biostudies-literature
Project description:The objective of the present hospital-based case-control study was to assess the association between glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphisms and susceptibility to pre-eclampsia (PE) in Shiraz (Fars province, southern Iran). A total of 200 healthy pregnant women and 151 pre-eclamptic women were included. The healthy control group was frequency matched with the age of the pre-eclamptic women. Control women had neither PE in current pregnancy nor history of pregnancies with PE previously. The genotypes of GSTT1 and GSTM1 polymorphisms were determined using a PCR-based method. Neither GSTM1 null genotype (OR=1.07, 95 % CI: 0.70-1.64, P=0.736) nor GSTT1 null genotype (OR=0.73, 95 % CI: 0.44-1.21, P=0.233) was associated with risk of PE. Association between combination genotypes and risk of PE was not significant. When family history was entered as a covariate in analysis, adjusted ORs revealed that neither GSTM1 nor GSTT1 polymorphisms was associated with risk of PE. For meta-analysis, we identified 5 eligible studies, including 1217 subjects (515 patients, and 702 healthy controls) in relation to the study polymorphisms and risk of PE. Our present meta-analysis indicated that there neither GSTM1 (OR=0.99, 95 % CI: 0.78-1.25, P=0.955) nor GSTT1 polymorphisms (OR=0.85, 95 % CI: 0.66-1.10, P=0.223) was associated with susceptibility to PE. Taken together it seems that the polymorphisms of GSTM1 and GSTT1 are not risk factors for PE. Further investigations adjusting for confounding factors are needed to confirm the present findings.
| S-EPMC5109005 | biostudies-literature
Project description:In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. Characterization of the GSTT1 polymorphism will thus enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals.
| S-EPMC1138152 | biostudies-other
Project description:BackgroundGlutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks.MethodsA meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association.ResultsThe null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14-1.21; for GSTT1: OR = 1.16; 95%CI = 1.11-1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19-3.24; for GSTT1: OR = 2.46; 95%CI = 1.83-3.32, respectively).ConclusionsThese findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.
| S-EPMC3826727 | biostudies-literature
Project description:Background Oxidative stress is an important issue in coronavirus disease 2019 (COVID-19). Considering that glutathione S-transferase P1 (GSTP1) is involved in cellular detoxification, it may play an important role in susceptibility to infection with SARS-CoV-2 and/or its outcome. In the present study, the association between the Ile105Val GSTP1 polymorphism (rs1695) and susceptibility to SARS-CoV-2 infection, as well as its outcome was investigated. Data on the prevalence (per 106 people), case-fatality (per 100 infected cases), and mortality (per 106 people) of COVID-19 and various potential confounders (the life expectancy at birth, density of medical doctors, density of nursing and midwifery personnel, and the gross national income per capita) were used. The latest data available for 45 countries were used for the study. Results In multivariate linear regression analyses, the Val105 allelic frequency showed positive association with the log-prevalence (partial r = 0.308, p = 0.042) and log-mortality of COVID-19 (partial r = 0.316, p = 0.037). The log-fatality did not show association with the allelic frequency. In the next step, only countries with the gross national income per capita more than $15,000 were included in the analysis. In the selected countries, the frequency of Val105 was positively associated with the log-prevalence (partial r = 0.456, p = 0.009) and log-mortality of COVID-19 (partial r = 0.544, p = 0.001). Conclusions The present findings indicate that countries with higher Val105 allelic frequency of the rs1695 polymorphism showed higher prevalence and mortality of COVID-19.
| S-EPMC7527247 | biostudies-literature
Project description:Glutathione S-transferase theta 1 (GSTT1) enzyme plays a key role in the neutralization of electrophilic compounds such as carcinogens. Herein, we aimed to evaluate GSTT1 deletion polymorphism and susceptibility to head and neck carcinoma (HNC) according to 107 articles in a systematic review with five analyses. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library from the beginning of each database until June 21, 2023, with no restrictions to identify pertinent articles. The RevMan 5.3 software was used to calculate the effect sizes, which were displayed as the odds ratio (OR) along with a 95% confidence interval (CI). Both the publication bias and sensitivity analyses were performed using the CMA 3.0 software. A trial sequential analysis (TSA) was conducted. Of the 1966 records retrieved from four databases, 107 articles were included in the analysis. The combined analysis revealed that the pooled OR was 1.28 (95% CI: 1.14 to 1.44; p-value < 0.0001). The pooled OR was highest in mixed ethnicity. Nasopharyngeal cancer had the highest OR (1.84), followed by oral cancer (OR = 1.20), and laryngeal cancer (OR = 1.17). Studies with less than 200 samples had a higher OR compared to those with 200 or more samples. The studies with a quality score of 7 or more had a higher OR compared to those with a score of less than 7. When both age and sex are considered, while the OR of 1.42 is significant, the high heterogeneity suggests caution in interpreting these results. There is no evidence of publication bias. TSA reported that the study does not have sufficient statistical power. This comprehensive meta-analysis revealed a significant association between the GSTT1 null genotype and an increased risk of HNC, with variations based on factors such as ethnicity, cancer type, sample size, control source, and quality score.
| S-EPMC11264357 | biostudies-literature
Project description:BackgroundThe association of the three Glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1 and GSTP1) genotypes with their individual susceptibilities to renal cell carcinoma (RCC) has not been well established. We performed a quantitative meta-analysis to assess the possible associations between the GSTM1, GSTT1 and GSTP1 genotypes and their individual susceptibilities to renal cell carcinoma.MethodsWe systematically searched the PubMed, CNKI and Embase databases to identify the relevant studies. Finally, 11 eligible studies were selected. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between the GSTs polymorphisms and the risk of RCC. Multiple subgroup analyses and quality assessment of the included studies were performed based on the available information.ResultsNone of the GSTs polymorphisms had a significant association with the RCC risk. Similar results were found in the subgroup analyses, except for the GSTs polymorphisms in the situations described below. The GSTM1 and GSTT1 active genotypes in subjects exposed to pesticides (GSTM1: OR = 3.44; 95% CI, 2.04-5.80; GSTT1: OR = 2.84; 95% CI, 1.75-4.60), most of the GSTs genotypes in Asian populations (GSTT1: OR = 2.39, 95% CI = 1.63-3.51; GSTP1: Dominant model: OR = 1.50, 95% CI = 1.14-1.99; Additive model: OR = 1.39, 95% CI = 1.12-1.73; AG vs. AA: OR = 1.47, 95% CI = 1.10-1.97; GG vs. AA: OR = 1.82, 95% CI = 1.07-3.09) and the dual null genotype of GSTT1-GSTP1 (OR = 2.84, 95% CI = 1.75-4.60) showed positive associations with the RCC risk.ConclusionOur present study provides evidence that the GSTM1, GSTT1 and GSTP1 polymorphisms are not associated with the development of RCC. However, more case-control studies are needed for further confirmation.
| S-EPMC3661732 | biostudies-literature
Project description:BackgroundA number of case-control studies were conducted to investigate the association of glutathione S-transferase (GST) genetic polymorphisms and hepatocellular carcinoma (HCC) risk. However, these studies have yielded contradictory results. We therefore performed a meta-analysis to derive a more precise estimation of the association between polymorphisms on GSTM1, GSTT1 and HCC.Methodology/prinicpal findingsPubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Potential sources of heterogeneity were also assessed by subgroup analysis and meta-regression. Funnel plots and Egger's linear regression were used to test publication bias among the articles. A total of 34 studies including 4,463 cases and 6,857 controls were included in this meta-analysis. In a combined analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.29, 95% CI: 1.06-1.58; P = 0.01) and GSTT1 (OR = 1.43, 95% CI: 1.22-1.68; P<10(-5)). Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. Significant results were found in East Asians and Indians when stratified by ethnicity; whereas no significant associations were found among Caucasians and African populations. By pooling data from 12 studies that considered combinations of GSTT1 and GSTM1 null genotypes, a statistically significant increased risk for HCC (OR = 1.88, 95% CI: 1.41-2.50; P<10(-4)) was detected for individuals with combined deletion mutations in both genes compared with positive genotypes.Conclusions/significanceThis meta-analysis suggests that the GSTM1 and GSTT1 null genotype may slightly increase the risk of HCC and that interaction between unfavourable GSTs genotypes may exist.
| S-EPMC3502401 | biostudies-literature