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The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma
Vesna ori , Marija Plje a-Ercegovac, , Marija Mati , , Biljana Krivi , Sonja uvakov, , Cane Tuli , , Jasmina Mimi -Oka, , Tatjana Simi
Journal of Medical Biochemistry , 2010, DOI: 10.2478/v10011-010-0025-8
Abstract: Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed subjects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active genotype is protective against RCC, whereas a GSTT1 active genotype increases RCC risk in occupationally exposed subjects.
Maternal Smoking,GSTM1 and GSTT1 Polymorphism and Susceptibility to Adverse Pregnancy Outcomes  [PDF]
Regina Grazuleviciene,Asta Danileviciute,Ruta Nadisauskiene,Jone Vencloviene
International Journal of Environmental Research and Public Health , 2009, DOI: 10.3390/ijerph6031282
Abstract: The objective of the study was to investigate the association between maternal smoking, GSTM1, GSTT1 polymorphism, low birth weight (LBW, < 2,500 g) and intra-uterine growth restriction (IUGR, < 2,500 g and gestation ≥ 37 weeks) risk. Within a prospective cohort study in Kaunas (Lithuania), a nested case-control study on LBW and IUGR occurrence among 646women with genotyping of GSTT1 and GSTM1 polymorphisms who delivered live singletons was conducted. Multivariate logistic regression analysis was used to study the association of maternal smoking and polymorphism in two genes metabolizing xenobiotics. Without consideration of genotype, light-smoking (mean 4.8 cigarettes/day) during pregnancy was associated with a small increase in LBW risk, adjusted OR 1.21; 95% CI 0.44 – 3.31. The corresponding odds for IUGR risk was 1.57; 95% CI 0.45 – 5.55. The findings suggested the greater LBW risk among light-smoking mothers with the GSTM1-null genotype (OR 1.91; 95% CI 0.43 – 8.47) compared to those with GSTM1-present genotype (OR 1.11; 95% CI 0.26 – 4.47). When both GSTM1 and GSTT1 genotypes were considered, the synergistic effect was found among smoking mothers: GSTT1-present and GSTM1-null genotype OR for LBW was 3.31; 95% CI 0.60-18.4 and that for IUGR was 2.47; 95% CI 0.31 – 13.1. However there was no statistically significant interaction between maternal smoking, GSTT1- present and GSTM1-null genotypes for LBW (OR 1.45; 95% CI 0.22 – 10.1, p = 0.66) and for IUGR (OR 1.10; 95% CI 0.10 – 12.6, p = 0.93).The results of this study suggested that smoking, even at a low-level, ought to be considered a potential risk factor for adverse birth outcomes and that genetic polymorphism may contribute to individual variation in tobacco smoke response.
CYP1A1, GSTM1 and GSTT1 Genetic Polymorphism in Egyptian Chronic Myeloid Leukemia Patients
Shereen Mahmoud,Dalia A. Labib,Rania H. Khalifa,Reham E. Abu Khalil
Research Journal of Immunology , 2010,
Abstract: The genetic polymorphism of xenobiotic metabolizing enzymes: phase I enzymes; cytochrome P450 (CYP1A1) and phase II enzymes; glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 30 chronic myeloid leukemia patients (CML) (19 females, 11 males; age (Mean±SD) 41.7±9.5 years) and 20 age and sex matched healthy controls. The frequency of CYP1A1 alleles and of GSTT1 and GSTM1 homozygous deletions was examined by PCR- RFLP and PCR methods, respectively, using blood samples. The relationship between these genotypes and risk of CML was assessed by means of Odds Ratio (OR) with 95% confidence limits. Present results showed that the frequency of the mutant allele CYP1A1*2A was found to be 3.3% in CML patients and 45% in controls (OR = 0.042, 95% CI: 0.005-0.373; p<0.001), suggesting that this polymorphic variant may be a protective factor against CML. The frequency of individuals carrying the GSTT1 null genotype was higher among CML patients (60%) compared to controls (15%) (OR = 8.5, 95% CI: 2.038-35.458; p = 0.002). Therefore, GSTT1 null genotype may be a risk factor for CML. Although, GSTM1 null genotype frequency was slightly higher in the patient group (46.7%) than in the controls (40%), this difference was not statistically significant (OR = 1.313, 95% CI: 0.417-4.131; p = 0.642). In conclusion this data suggests that polymorphic CYP1A1 and GSTT1 genes appear to affect susceptibility to CML.
Polymorphism of GSTM1 and GSTT1 genes in prostate cancer: A study from North India  [cached]
Mittal Rama Devi,Srivastava D,Mandhani A,Kumar A
Indian Journal of Cancer , 2004,
Abstract: BACKGROUND : Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. The genetic polymorphisms of GSTM1 and GSTT1 genes have been studied earlier to evaluate the relative risk of various cancers. AIM, SETTING AND DESIGN : In the present study, we examined the association of the GSTM1 and GSTT1 gene polymorphisms with sporadic prostate cancer patients in north Indian population. MATERIAL AND METHODS : This case control study was undertaken over a period of 24 months and included 103 prostate cancer patients and 117 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. STATISTICAL ANALYSIS : Difference in genotype prevalence and association between case and control group were assessed by the Chi square and Fisher Exact tests. RESULTS : Frequencies of null genotypes in GSTT1 and GSTM1, was 11% (13/117) and 30% (35/117) respectively in control individuals. The frequencies of GSTT1 and GSTM1 null genotypes in prostate cancer patients were 34% (35/103) and 53% (55/103) respectively. CONCLUSION : Our study demonstrates that the null genotypes of GSTT1 and GSTM1 are substantially at higher risk for prostate carcinoma as compared to the normal healthy controls. The GSTT1 and GSTM1 null genotypes did not show significant association with tobacco usage in prostate cancer patients. However, the null genotypes were significantly stratified in 50-60 year-old patients when incidence of prostate cancer is high.
Association between GSTM1 and GSTT1 polymorphisms and susceptibility to methamphetamine dependence
Mohammad Rashid Khalighinasab, Khyber Saify, Mostafa Saadat
Molecular Biology Research Communications , 2015,
Abstract: Glutathione S-transferases (GSTs; EC: 2.5.1.18) are ubiquitous multifunctional enzymes, which play a key role in cellular detoxification. Functional genetic polymorphisms in genes encoding GSTM1 (a member of GST class mu; OMIM: 138350), and GSTT1 (a member of GST class theta; OMIM: 600436) have been well defined. The functional null alleles of GSTM1 and GSTT1 represent deletions of GSTM1 and GSTT1 genes, respectively. The aim of the present study is to investigate the association between GSTM1 and GSTT1 polymorphisms and methamphetamine dependence. The present population-based case-control study was performed in Shiraz (southern Iran). In total, 52 methamphetamine dependence (11 females, 41 males) and 635 healthy controls (110 females, 525 males) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Neither GSTM1 (OR=0.92, 95% CI: 0.52-1.61, P=0.771) nor GSTT1 (OR=0.71, 95% CI: 0.33-1.54, P=0.381) null genotypes were significantly associated with risk of methamphetamine dependence. It should be noted that although there was no association between the GSTM1 null genotype and risk of methamphetamine dependence, in both genders, there was significant interaction between gender and GSTM1 polymorphism (P=0.029). The combination genotypes of the GSTM1 and GSTT1 polymorphisms revealed that the genotypes of these two polymorphisms had no additive effect in relation to the susceptibility to methamphetamine dependence. The present study revealed that genetic polymorphisms of GSTT1 and GSTM1 are not risk factors for methamphetamine dependence.
No association between GSTM1 and GSTT1 genetic polymorphisms and susceptibility to opium sap dependence
Khyber Saify, Mohammad Rashid Khalighinasab, Mostafa Saadat
Molecular Biology Research Communications , 2016,
Abstract: Glutathione S-transferases (GSTs; EC: 2.5.1.18) are a ubiquitous family of eukaryotic and prokaryotic phase II metabolic isozymes. Genes encoding GSTM1 (OMIM: 138350), and GSTT1 (OMIM: 600436) are members of class mu and theta, respectively. The most common polymorphism in the GSTM1 is a deletion of the whole GSTM1 gene with a lack of enzyme activity. A homozygous deletion in the GSTT1 has also been reported (null genotypes of GSTT1). The aim of the present study was to investigate the association between GSTM1 and GSTT1 polymorphisms and risk of dependency to opium sap. The present study was performed in Shiraz (southern Iran). In total, 71 males dependent to opium sap and 590 healthy males (as a control group) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Our data indicate that neither GSTM1 (OR=0.78, 95% CI: 0.47-1.27, P=0.325) nor GSTT1 (OR=1.25, 95% CI: 0.70-2.21, P=0.442) null genotypes significantly associated with the risk of opium sap dependence. There is no additive effect of the null genotypes of GSTT1 and GSTM1 in relation to the risk of dependency to opium sap. The present study indicated that the null genotypes of GSTT1 and GSTM1 are not risk factor for opium sap dependence.
Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies  [PDF]
Mancheng Gong, Wenjing Dong, Zhirong Shi, Yangyang Xu, Wenjun Ni, Ruihua An
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050587
Abstract: Background and Objectives The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy. Methods Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms. Results Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405–1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345–1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067–2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596–1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96–1.2251) and the PCa risk. Conclusions Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.
Investigating Frequency of GSTT1 and GSTM1 Genes Null Genotype in Men with Varicocele and Its Association with the Sperm Parameters
M Dehghani,AR Vahidi,MR Moin,F Haghiroalsadat
Journal of Shahid Sadoughi University of Medical Sciences , 2012,
Abstract: Introduction: GSTM and GSTT are subclasses of glutathione s-transferase that is present on human sperm surface and plays an important role against oxidative stress. This study aimed to investigate the polymorphisms of GSTT1 and GSTM1 in regard to sperm parameters. Methods: This case-control study involved 46 men with varicocele and 48 men without varicocele. Semen analyses were carried out according to WHO guidelines. Blood DNA was extracted using salting out procedures. Polymorphism of GSTT1 and GSTM1 genes was determined trough multiplex-PCR respectively. Results: Frequencies of GSTM1 null genotype in men with varicocelc and men without varicocele groups were 60.9 and 41.7 respectively. There were no statistically significant differences between Gstm1 null and positive genotype in two groups (p>0.05). Frequencies of gstt1 null genotype in case and control groups were 47.8 and 50 respectively. There were no statistically significant relationship between gstt1 null and positive genotype in two groups (p>0.05). Conclusions: Deficiency of enzyme activity in gstm1 null genotype did not affect morphology as well as slow and quick progressive of sperm but caused the significant decrease in count of sperm between gstm1 null and positive genotype. In the case of gstt1, gstt1 null genotype did not affect sperm parameters that may be related to compensate activity of other genes in this super family.
Evaluation of Glutathione S-Transferase GSTM1 and GSTT1 Deletion Polymorphisms on Type-2 Diabetes Mellitus Risk  [PDF]
Denise S. Pinheiro, César R. Rocha Filho, Cláudia A. Mundim, Paulo de Marco Júnior, Cirano J. Ulhoa, Angela A. S. Reis, Paulo C. Ghedini
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076262
Abstract: Background Due to the activity of GSTs in the detoxification of oxidative stress products, deletion polymorphisms of GSTM1 and GSTT1 may contribute to susceptibility to T2DM, since B-cells express very low levels of antioxidant enzymes. Recently, some studies have shown an association between GSTM1-null/GSTT1-null genotypes and an increased susceptibility to T2DM. A relationship between these polymorphisms and changes in the clinical parameters of diabetic patients has also been investigated. However, the results diverge considerably among the studies. Thus, this case-control study was designed to contribute to existing knowledge, as there are no studies on this issue performed in the Brazilian population. Methods and Findings A total of 120 patients and 147 healthy individuals were included in this study. GSTT1 and GSTM1 deletion polymorphisms were genotyped by multiplex SYBR Green Real-Time PCR. The GSTT1-null genotype conferred a 3.2-fold increased risk to T2DM relative to the present genotype. There was no association between GSTM1-null and T2DM risk. In diabetic patients, GSTT1-null conferred higher levels of triglycerides and VLDL-cholesterol, while GSTM1-null was associated with increased levels of fasting blood glucose, glycated hemoglobin and blood pressure. We emphasized a necessity for applying log-linear analysis in order to explore an interaction between these polymorphisms properly. Conclusion These results suggest that the GSTT1 polymorphism may play an important role in the pathogenesis of T2DM in the Brazilian population. This gene could then be added to a set of genetic markers to identify individuals with an increased risk for developing T2DM and complications associated with dyslipidemia in diabetic patients. Although there was no association of GSTM1 deletion polymorphism with susceptibility to T2DM, the influence of this polymorphism on important clinical parameters related to glycemia and blood pressure levels was verified. This finding suggests that both GSTM1-null and GSTT1-null may contribute to the clinical course of T2DM patients.
GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening
Aguiar, Ernestina Silva de;Giacomazzi, Juliana;Schmidt, Aishameriane Venes;Bock, Hugo;Saraiva-Pereira, Maria Luiza;Schuler-Faccini, Lavínia;Duarte Filho, Dakir;Santos, Pollyanna Almeida Costa dos;Giugliani, Roberto;Caleffi, Maira;Camey, Suzi Alves;Ashton-Prolla, Patrícia;
Revista Brasileira de Epidemiologia , 2012, DOI: 10.1590/S1415-790X2012000200002
Abstract: genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione s-transferases (gstm1, gstt1, and gstp1) superfamily have been associated with an increased risk for breast cancer (bc). considering the high incidence of bc in the city of porto alegre in southern brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in gstm1, gstt1, and gstp1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. molecular tests were performed using the multiplex polymerase chain reaction (pcr) for gstm1 and gstt1, and quantitative pcr for gstp1 polymorphisms. overall, the frequencies of gstm1 and gstt1 null genotypes were 45% and 21%, respectively. for gstp1 polymorphism, genotypic frequencies were 44% for the ile/ile genotype, 44% for the ile/val genotype, and 12% for val/val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. there was a statistically significant association between the combined gstm1 and gstt1 null genotypes (m-/t-) and mammographic density in post menopausal women (p = 0.031). when the gstt1 null (t-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). these findings suggest an association of gstm1 and gstt1 null genotypes with mammographic density.
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