Dataset Information

GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: A genetic association study in Brazilian patients.

ABSTRACT:

Background

The role of oxidative stress in schizophrenia has been demonstrated, particularly in subjects with treatment-resistant schizophrenia (TRS). In such patients, the decreased levels of antioxidants in conjunction with the increased generation of reactive oxygen species in the brain exposes the neurons to a higher risk of damage.

Methods and findings

We evaluated the association of deletion polymorphisms of two genes of the antioxidant Glutathione S-Transferase family, GSTT1 and GSTM1, with susceptibility to TRS. A total of 54 TRS patients (mean age 38.7 years) and 78 healthy control subjects (mean age 39.0 years) were enrolled in this study. The subjects were matched by sex, age, and smoking and alcohol consumption habits. In the case group, the frequencies of GSTT1-null and GSTM1-null genotypes were 24.1 and 51.9%, respectively, whereas for the control group, the frequencies were 12.8 and 46.2%, respectively. Analysis performed with respect to the risk of developing TRS associated with the GSTT1 and GSTM1 deletion polymorphisms, resulted in odds ratio (OR) values of 2.1 and 1.2, respectively. However, the association was not found to be significant (p = 0.1229 and p = 0.5916, respectively). The analysis performed with respect to the combined genotypes of GSTT1 and GSTM1 revealed that the double-null genotype confers a 4.6-fold increased risk of developing TRS (p = 0.0412).

Conclusion

The results of the present study indicate that a combination of GST deficiencies may play a role in enhanced susceptibility to TRS, and the present genotype of one of these genes may buffer the deficiency caused by the lack (null genotype) of the other. The results suggest that combined deletion polymorphisms of GSTT1 and GSTM1 can have implications in the prediction of the clinical course of the disease.

SUBMITTER: Pinheiro DS

PROVIDER: S-EPMC5570380 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: A genetic association study in Brazilian patients.

Pinheiro Denise S DS Santos Rodrigo da S RDS de Brito Rodrigo B RB Cruz Aline Helena da S AHDS Ghedini Paulo C PC Reis Angela A S AAS Reis Angela A S AAS

PloS one 20170824 8

<h4>Background</h4>The role of oxidative stress in schizophrenia has been demonstrated, particularly in subjects with treatment-resistant schizophrenia (TRS). In such patients, the decreased levels of antioxidants in conjunction with the increased generation of reactive oxygen species in the brain exposes the neurons to a higher risk of damage.<h4>Methods and findings</h4>We evaluated the association of deletion polymorphisms of two genes of the antioxidant Glutathione S-Transferase family, GSTT ...[more]

PMID: 28837637

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Project description:BackgroundIt is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC.MethodsWe searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0).ResultsThe pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null.ConclusionsOur study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.

Project description:Preventing the ototoxicity caused by cisplatin is a major issue yet to be overcome. Useful preventive treatments will soon be available. Consequently, the next step is to filter out those patients who are more prone to develop ototoxicity. The aim of this study was to prospectively evaluate potential predictive markers of acute ototoxicity as determined by measures of distortion product otoacoustic emissions (DPOAEs). A total of 118 patients from our previous DPOAE analysis were put under evaluation. Ototoxic cases were divided according to unilateral (n = 45) or bilateral (n = 23) involvement. The clinicopathological characteristics, hearing test results, germline GSTT1, GSTM1, and GSTP1 polymorphisms, and common laboratory parameters were included in the new analysis. Univariate and multivariate statistical tests were applied. According to multivariate logistic regression, the only independent predictor of unilateral ototoxicity (vs. non-affected) was a GSTM1 null genotype (OR = 4.52; 95%CI = 1.3-16.3), while for bilateral damage, the GSTT1 null genotype (OR = 4.76; 1.4-16) was a predictor. The higher starting serum urea level was characteristic of bilateral ototoxicity; however, the only independent marker of bilateral (vs. unilateral) ototoxicity was the presence of GSTT1 null genotype (OR = 2.44; 1.23-4.85). Different processes, involving the GSTM1 and GSTT1 genotypes, respectively, govern the development of acute unilateral and bilateral ototoxicities. Further research is needed to clarify these processes. Based on the above findings, patients whom are at risk may be selected for otoprotective therapies. KEY MESSAGES: The acute ototoxicity was determined by DPOAE in 118 testicular cancer patients. GSTM1 null was the only marker of unilateral ototoxicity (vs. non-affected). The only marker of bilateral hearing loss (vs. non-affected) was the GSTT1 null. GSTT1 null was also the marker of bilateral vs. unilateral ototoxicity. A high-risk group may be selected for new, individualized otoprotective treatment.

Dataset Information

GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: A genetic association study in Brazilian patients.

Background

Methods and findings

Conclusion

Publications

GSTM1/GSTT1 double-null genotype increases risk of treatment-resistant schizophrenia: A genetic association study in Brazilian patients.

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