Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. Glutathione S-transferases (GSTs) is group of multifunction antioxidant enzyme can be used as important biomarkers for DM.. GSTM1, T1 genes variant polymorphism result in decreased or loss of enzyme activity. AIM: The study aimed to evaluate the role of GSTM1 and GSTT1 gene polymorphism in the risk of developing T2DM. METHODS: GSTM1 and GSTT1 polymorphisms were genotyped in 87 T2DM patients and 87 healthy control group to analyze their association with T2DM susceptibility by using multiplex Polymerase Chain Reaction (PCR). PCR products were electrophoresed using agarose 2%. Odds ratio (OR) with 95% confidence interval (CI) and P value were calculated using SPSS software (version 21.0). RESULTS: The genotype distribution of GSTM1 and GSTT1 were not different between T2DM patients and healthy control group (p = 0.542, OR= 0.780, CI 95%=0.350-1.737 and p=0.879, OR=1.047, CI 95%=0.577-1.903). The genotype distribution of combination of GSTM1 and GSTT1 were also not not different between T2DM patients and healthy control group (p = 0.640, OR= 0.640, CI 95%=0.224-1.83 and p=0.551, OR=0.721, CI 95%=0.245-2.120. CONCLUSION: In summary, this study showed that GSTT1 null, GSTM1 null, the combination of GSTM1 null and GSTT1 null genotype or combination of GSTM1 null and GSTT1 positive (or contrary) did not have any risk of developing T2DM at Universitas Sumatera Utara Hospital, Medan.

Association of Polymorphisms in the Glutathione S-Transferase Theta-1 Gene with Cirrhosis and Hepatocellular Carcinoma in Brazilian Patients with Chronic Hepatitis C

Oxidative stress contributes to hepatitis C virus (HCV)–induced liver damage. Host genetic factors may be involved in progression of HCV infection. The present study was conducted to determine the influence of glutathione S-transferase (GST)-M1 and T1 gene polymorphisms during different stages of HCV infection, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The study population comprised 190 patients (47 with chronic hepatitis, 83 with cirrhosis (without HCC), and 60 with HCC). GSTM1 and GSTT1 gene polymorphisms were analyzed via multiplex polymerase chain reaction. The GSTT1-null genotype was more commonly detected in patients with cirrhosis (n = 17; 20.5%) and HCC (n = 13; 21.7%) than those with chronic hepatitis (n = 3; 6.4%). The differences in GSTT1-null genotype frequencies were significant for cirrhosis vs. chronic hepatitis (odds ratio, OR, 3.778 (95% confidence interval, CI, 1.045–13.659); p = 0.043) and HCC vs. chronic hepatitis (OR, 4.057 (95% CI, 1.083–15.201); p = 0.038) groups. However, the incidence of individual GSTM1-null or combined GSTM1/GSTT1 double-null genotypes did not vary significantly between the groups. Our collective findings support the utility of the GSTT1-null genotype as a useful biomarker for liver disease progression in Brazilian patients with chronic hepatitis C.

Polymorphisms of CYP1A1*4 and GST as Susceptibility and Prognostic Genes for Acute Myeloid Leukemia

Introduction: Associations between polymorphisms for genes encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the study is to investigate the influence of cytochromes P450 (CYP1A1*4) and Glutathione S-transferases (GSTs) (T1 and M1) gene polymorphisms in susceptibility to acute myeloid leukemia (AML) as well as their prognostic role for the treatment outcome in AML patients. Material and Methods: This study included 65 individuals classified as healthy controls and newly diagnosed AML patients. BMA and immunophenotyping assay by flowcytometry were done at D1 and D14 following treatment induction to assess the complete remission or non response to treatment in AML patients. The CYP1A1*4 and of GSTT1and GSTM1 genotypes were examined using polymerase chain reaction (PCR)-based methods. Results: A higher prevalence of the CYP1A1*4 (CA and AA) genotype was found in AML patients than in controls (37% vs 23.3%, OR =3.25, 95% CI. 1.01-10.46, p=0.05). GSTT1 null genotype were also more frequent in AML patients than in controls (58% vs 26.7%, OR = 3.79, 95% CI 1.11-12.87, p=0.03). The combination of GSTT1 null genotype and CYP1A1 *4 (AA) genotype further increased the risk of AML (OR =12.66, 95% CI 1.19-128.6, p=0.03. Conclusion: GSTT1 null genotype appears to modulate individual’s susceptibility of AML patients to treatment response, especially when combined with CYP1A1*4 (AA) genotype suggesting gene-gene interactions.

Influence of GSTT1 and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Retinopathy Risk in The Chinese Population: A Case Control Study

Background: Studies have revealed the association of glutathione S-transferases (GSTM1 and GSTT1) deletion (null) polymorphism with the risks of developing type 2 diabetes mellitus (T2DM) and its complications. The present study aimed to investigate the relationship between GSTT1/ GSTP1 gene polymorphisms and the risks of T2DM and diabetic retinopathy (DR) in a Chinese population.Methods: A total of 336 subjects with T2DM and a defined ophthalmologic status were recruited from the Second People’s Hospital of Yunnan Province between June 2014 and October 2016. Seventy-two age-matched healthy controls were also enrolled. Physical examinations and laboratory tests were performed. The frequencies of GSTT1 and GSTP1 genotypes in all participants were determined by PCR and PCR-restriction fragment length polymorphisms (PCR–RFLP), respectively.Results: Compared with healthy controls, the GSTT1-null genotype was significantly more common in diabetic patients with or without DR (all P < 0.05). However, the frequency of the GSTP1 genotype (AA, GA, GG) was comparable between the two groups. Furthermore, neither the GSTP1 nor GSTT1 genetic polymorphism was associated with the development of DR. In the present study, the risk of developing T2DM was significantly higher in subjects carrying the combined heterozygous GSTP1 (AG) and null GSTT1 genotypes (OR=0.40, 95% CI=0.21-0.74, P=0.02).Conclusions: The deletion of the GSTT1 genotype was associated with a higher risk of developing T2DM, whether alone or in combination with GSTP1, indicating that the null genotype of GSTT1 may serve as a potential biomarker for T2DM in the Chinese population, which is helpful for clinicians to make more effective risk-based decisions.

Influence of GSTT1 and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Retinopathy Risk in The Chinese Population: A Case Control Study

Background: Studies have revealed the association of glutathione S-transferases (GSTM1 and GSTT1) deletion (null) polymorphism with the risks of developing type 2 diabetes mellitus (T2DM) and its complications. The present study aimed to investigate the relationship between GSTT1/ GSTP1 gene polymorphisms and the risks of T2DM and diabetic retinopathy (DR) in a Chinese population.Methods: A total of 336 subjects with T2DM and a defined ophthalmologic status were recruited from the Second People’s Hospital of Yunnan Province between June 2014 and October 2016. Seventy-two age-matched healthy controls were also enrolled. Physical examinations and laboratory tests were performed. The frequencies of GSTT1 and GSTP1 genotypes in all participants were determined by PCR and PCR-restriction fragment length polymorphisms (PCR–RFLP), respectively.Results: Compared with healthy controls, the GSTT1-null genotype was significantly more common in diabetic patients with or without DR (all P < 0.05). However, the frequency of the GSTP1 genotype (AA, GA, GG) was comparable between the two groups. Furthermore, neither the GSTP1 nor GSTT1 genetic polymorphism was associated with the development of DR. In the present study, the risk of developing T2DM was significantly higher in subjects carrying the combined heterozygous GSTP1 (AG) and null GSTT1 genotypes (OR=0.40, 95% CI=0.21-0.74, P=0.02).Conclusions: The deletion of the GSTT1 genotype was associated with a higher risk of developing T2DM, whether alone or in combination with GSTP1, indicating that the null genotype of GSTT1 may serve as a potential biomarker for T2DM in the Chinese population, which is helpful for clinicians to make more effective risk-based decisions.

Influence of GSTT1 and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Retinopathy Risk in the Chinese Population: A Case Control Study

Background: Studies have revealed the association of glutathione S-transferases (GSTM1 and GSTT1) deletion (null) polymorphism with the risks of developing type 2 diabetes mellitus (T2DM) and its complications. The present study aimed to investigate the relationship between GSTT1/ GSTP1 gene polymorphisms and the risks of T2DM and diabetic retinopathy (DR) in a Chinese population.Methods: A total of 336 subjects with T2DM and a defined ophthalmologic status were recruited from the Second People’s Hospital of Yunnan Province between June 2014 and October 2016. Seventy-two age-matched healthy controls were also enrolled. Physical examinations and laboratory tests were performed. The frequencies of GSTT1 and GSTP1 genotypes in all participants were determined by PCR and PCR-restriction fragment length polymorphisms (PCR–RFLP), respectively.Results: Compared with healthy controls, the GSTT1-null genotype was significantly more common in diabetic patients with or without DR (all P < 0.05). However, the frequency of the GSTP1 genotype (AA, GA, GG) was comparable between the two groups. Furthermore, neither the GSTP1 nor GSTT1 genetic polymorphism was associated with the development of DR. In the present study, the risk of developing T2DM was significantly higher in subjects carrying the combined heterozygous GSTP1 (AG) and null GSTT1 genotypes (OR=0.40, 95% CI=0.21-0.74, P=0.02).Conclusions: The deletion of the GSTT1 genotype was associated with a higher risk of developing T2DM, whether alone or in combination with GSTP1, indicating that the null genotype of GSTT1 may serve as a potential biomarker for T2DM in the Chinese population, which is helpful for clinicians to make more effective risk-based decisions.

Individual and combined effects of GSTM1 and GSTT1 polymorphisms on colorectal cancer risk: an updated meta-analysis

Background. The presence or absence of glutathione S-transferase M1 gene (GSTM1) and glutathione S-transferase T1 gene (GSTT1) polymorphisms, and their combined effects have been suggested as a risk factor for colorectal cancer (CRC). However, the results are inconsistent. Objectives. An updated meta-analysis was performed to solve the controversy. Methods. Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were used. Results. Overall, the GSTM1 null genotype was associated with an increased CRC risk in Caucasians (odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.05–1.23), Asians (OR = 1.19, 95% CI: 1.08–1.32), high-quality studies (OR = 1.12, 95% CI: 1.06–1.18). Moreover, the GSTM1 null genotype was also associated with an increased colon cancer risk (OR = 1.32, 95% CI: 1.16–1.51). The GSTT1 null genotype was also associated with an increased CRC risk in Asians (OR = 1.08, 95% CI: 1.02–1.15) and Caucasians (OR = 1.24, 95% CI: 1.09–1.41). Moreover, The GSTT1 null genotype was associated with an increased rectal cancer risk (OR = 1.13, 95% CI: 1.01–1.27, I2 = 8.3%) in subgroup analysis by tumor location. Last, the GSTM1 null/GSTT1 null genotype was associated with an increased CRC risk in Asians. Conclusion. This meta-analysis indicates that the GSTM1 and GSTT1 null genotypes are associated with increased CRC risk in Asians and Caucasians, and the GSTM1 null/GSTT1 null genotype was associated with increased CRC risk in Asians.

Influence of Polymorphisms of DNA Repair and GST Genes on Genotoxic Damage and Mutagen Sensitivity in Workers Occupationally Exposed to Very Low Doses of Ionizing Radiation

The study investigated the influence of genetic polymorphisms of the enzymes for DNA repair and detoxification of reactive intermediates on spontaneous and bleomycin-induced (BLM) genotoxic damage in 43 workers exposed to very low doses of ionizing radiation (IR) (mean cumulative dose 5.31 mSv) and 43 subjects with no occupational exposure to IR (controls). In all the subjects examined, the frequency of chromosome aberrations (CAs) and micronuclei (MN), both spontaneous and BLM-induced, the Comet assay parameters (tail intensity), the genotypic variants of the DNA repair enzymes XRCC1 (Arg194Trp, Arg280His, Arg399Gln), XRCC3 (Thr241Met), XPD (Lys751Gln), and of the detoxification enzymes GSTM1 and GSTT1 (null genotype) and BLMH (A1450G) were determined. Among the biomarkers considered, only the frequency of total CAs (p < 0.05), and in particular of chromosome breaks (p < 0.01), was found to be significantly higher in the exposed workers than the controls. The frequency of spontaneous MN was higher in subjects with at least one allelic variant in XRCC1 than in carriers of the wild-type, but again only in exposed workers (p = 0.046). Linear regression analysis showed a positive dependency of the frequency of spontaneous chromosome breaks on occupational exposure, and a dependency of the frequency of BLM-induced MN negative on occupational exposure and positive on alcohol consumption and the null GSTM1 genotype. In conclusion, the frequency of chromosome breaks seems to be a useful cytogenetic biomarker for exposure to very low doses of IR, while only the combined effect of different gene variants or genetic, occupational, and lifestyle habits factors seems to be able to modulate the genotoxic effect of very low doses of IR.