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Suthar PC, Purkait P, Uttaravalli K, Sarkar BN, Ameta R, Sikdar M. Glutathione S-transferase M1 and T1 null genotype frequency distribution among four tribal populations of western India. J Genet 2018. [DOI: 10.1007/s12041-018-0888-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Shu W, Guan S, Yang X, Liang L, Li J, Chen Z, Zhang Y, Chen L, Wang X, Huang M. Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4-hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus. Br J Clin Pharmacol 2015; 81:327-40. [PMID: 26456622 DOI: 10.1111/bcp.12800] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 10/01/2015] [Accepted: 10/09/2015] [Indexed: 11/29/2022] Open
Abstract
AIMS The aim of the study was to investigate the combined impact of genetic polymorphisms in key pharmacokinetic genes on plasma concentrations and clinical outcomes of cyclophosphamide (CPA) in Chinese patients with systemic lupus erythematosus (SLE). METHODS One hundred and eighty nine Chinese SLE patients treated with CPA induction therapy (200 mg, every other day) were recruited and adverse reactions were recorded. After 4 weeks induction therapy, 128 lupus nephritis (LN) patients continued to CPA maintenance therapy (200-600 mg week(-1)) for 6 months, and their clinical outcomes were recorded. Blood samples were collected for CYP2C19, CYP2B6, GST and PXR polymorphism analysis, as well as CPA and its active metabolite (4-hydroxycyclophosphamide (4-OH-CPA)) plasma concentration determination. RESULTS Multiple linear regression analysis revealed that CYP2B6 -750 T > C (P < 0.001), -2320 T > C (P < 0.001), 15582C > T (P = 0.017), CYP2C19*2 (P < 0.001) and PXR 66034 T > C (P = 0.028) accounted for 47% of the variation in 4-OH-CPA plasma concentration. Among these variants, CYP2B6 -750 T > C and CYP2C19*2 were selected as the combination genetic marker because these two SNPs contributed the most to the inter-individual variability in 4-OH-CPA concentration, accounting for 23.6% and 21.5% of the variation, respectively. Extensive metabolizers (EMs) (CYP2B6 -750TT, CYP2C19*1*1) had significantly higher median 4-OH-CPA plasma concentrations (34.8, 11.0 and 6.6 ng ml(-1) for EMs, intermediate metabolizers (IMs) and poor metabolizers (PMs), P < 0.0001), higher risks of leukocytopenia (OR = 7.538, 95% CI 2.951, 19.256, P < 0.0001) and gastrointestinal toxicity (OR = 7.579, 95% CI 2.934, 19.578, P < 0.0001), as well as shorter median time to achieve complete remission (13.2, 18.3 and 23.3 weeks for EMs, IMs and PMs, respectively, P = 0.026) in LN patients than PMs (CYP2B6 -750CC, CYP2C19*2*2) and IMs. CONCLUSIONS Our findings have indicated that genetic markers of drug metabolizing enzymes could predict the 4-hydroxylation, adverse reactions and clinical efficacy of CPA. This is a necessary first step towards building clinical tools that will help assess clinical benefit and risk before undergoing CPA treatment in Chinese SLE patients.
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Affiliation(s)
- Wenying Shu
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006.,Department of Pharmacy, Cancer Center of Guangzhou Medical University, Guangzhou, 510182
| | - Su Guan
- School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, 510006
| | - Xiuyan Yang
- Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Liuqin Liang
- Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Jiali Li
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
| | - Zhuojia Chen
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
| | - Yu Zhang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
| | - Lingyan Chen
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
| | - Xueding Wang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
| | - Min Huang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006
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Liu H, Ding L, Zhang F, Zhang Y, Gao X, Hu P, Bi H, Huang M. The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases. J Pharmacol Sci 2015; 129:95-100. [DOI: 10.1016/j.jphs.2015.02.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Revised: 02/02/2015] [Accepted: 02/24/2015] [Indexed: 01/26/2023] Open
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Yuan L, Liu J, Dong L, Cai C, Wang S, Wang B, Xiao R. Effects of APOE rs429358, rs7412 and GSTM1/GSTT1 Polymorphism on Plasma and Erythrocyte Antioxidant Parameters and Cognition in Old Chinese Adults. Nutrients 2015; 7:8261-73. [PMID: 26404360 PMCID: PMC4632411 DOI: 10.3390/nu7105391] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/10/2015] [Accepted: 08/27/2015] [Indexed: 11/19/2022] Open
Abstract
Apolipoprotein E (APOE) and oxidative damage were correlated with the risk of Alzheimer’s disease (AD). Glutathione S-transferase (GST) polymorphism was proved to be associated with body antioxidant capacity and involved in the oxidative damage related chronic diseases. To explore the combined effects of APOE rs429358, rs7412 and GSTM1/T1 polymorphism on antioxidant parameters and cognition in old Chinese adults, a community-based cross-sectional study was carried out in 477 Chinese adults aged from 55 to 75. Information on demography and lifestyle of the participants was collected with a questionnaire. Cognitive function was measured by using a Montreal Cognitive Assessment (MoCA) test. Fasting venous blood samples were collected for APOE rs429358, rs7412 and GSTM1/T1 genotyping, and parameter measurement. No association of APOE rs7412, rs429358 and GSTM1/T1 polymorphisms with cognition was detected in the old Chinese adults. APOE rs429358, rs7412 polymorphism was mainly associated with plasma α-tocopherol, low density lipoprotein cholesterol (LDL-C) and plasma total antioxidant capacity (T-AOC) levels (p < 0.05). Interaction of APOE rs429358 and GSTT1 genotype on the plasma triglyceride (TG) level and erythrocyte catalase (CAT) and GST enzyme activities were detected (p < 0.05). The subjects with APOE rs429358 T/C + C/C and GSTT1− genotype were found to have the highest plasma TG level, erythrocyte CAT enzyme activity, and the lowest GST enzyme activity compared to subjects with other genotypes (p < 0.05). Lowest erythrocyte CAT enzyme activity and highest glutathione peroxidase (GSH-Px) enzyme activity were detected in the subjects with APOE rs7412 T/C + T/T and GSTM1+ genotype as compared with subjects with other genotypes. The levels of plasma and erythrocyte antioxidant parameters were APOE genotype associated. GSTM1 or GSTT1 genotype modified the influence of APOE rs7412, rs429358 polymorphism on antioxidant parameters.
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Affiliation(s)
- Linhong Yuan
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
| | - Jinmeng Liu
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
| | - Li Dong
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
| | - Can Cai
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
| | - Sisi Wang
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
| | - Bo Wang
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
| | - Rong Xiao
- School of Public Health, Nutrition and Food Hygiene Department, Capital Medical University, Beijing 100069.
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An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1 and GSTT1) Polymorphisms to Age-Related Cataract. J Ophthalmol 2015; 2015:103950. [PMID: 25692031 PMCID: PMC4322823 DOI: 10.1155/2015/103950] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 11/21/2014] [Indexed: 01/13/2023] Open
Abstract
Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057–1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598–0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137–1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.
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Yuan L, Ma W, Liu J, Meng L, Liu J, Li S, Han J, Liu Q, Feng L, Wang C, Xiao R. Effects of GSTM1/GSTT1 gene polymorphism and fruit & vegetable consumption on antioxidant biomarkers and cognitive function in the elderly: a community based cross-sectional study. PLoS One 2014; 9:e113588. [PMID: 25420021 PMCID: PMC4242636 DOI: 10.1371/journal.pone.0113588] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Accepted: 10/27/2014] [Indexed: 01/01/2023] Open
Abstract
Background It was reported that Glutathione S-transferase (GST) gene polymorphism and fruit and vegetable (FV) intake were associated with body antioxidant capacity. The oxidative/anti-oxidative imbalance played an important role in the pathogenesis of AD. However, the association of GST genotype, dietary FV consumption with body antioxidant biomarkers and cognitive function in the elderly is not clear. Objective The aim of the present study was to determine the association of GST genotype, and dietary FV intake, with antioxidant biomarkers and cognitive function in the elderly. Methods Food frequency questionnaire was used to collect data of dietary FV intakes in 504 community dwelling elderly aged from 55 to 75 years old. GSTM1 and GSTT1 genotypes were determined by using multiple-PCR method. Plasma and erythrocyte antioxidant biomarkers were measured. Cognitive function was measured by using Montreal Cognitive Assessment. Statistical analysis was applied for exploring the association of GST genotype and FV intake with antioxidant biomarkers level and cognitive function in the elderly. Results Individual GSTM1 or GSTT1 gene deletion affects body antioxidant biomarkers levels, including erythrocyte GST activity, plasma total antioxidant capacity, and glutathione levels. GSTM1and/or GSTT1 gene deletion have no effects on cognitive function in the surveyed participants. The effect of GST genotype on antioxidant biomarkers are FV intake dependent. There is interaction of FV intake and GST genotype on cognitive function in the elderly. Conclusion GST genotype or daily FV consumption impact body antioxidant biomarkers, but not cognitive function in the elderly. There were combined effects of GST genotype and FV consumption on cognitive function in the elderly population. Large scale perspective population study is required to explore the association of GST genetic polymorphism, FV consumption and antioxidant biomarkers and cognitive function in the elderly.
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Affiliation(s)
- Linhong Yuan
- School of Public Health, Capital Medical University, Beijing, P.R.China
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, P.R. China
| | - Weiwei Ma
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Jinmeng Liu
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Liping Meng
- Institute of Nutrition and Food Safety, Chinese Center for Disease Control and Prevention, Beijing, P.R. China
| | - Jixia Liu
- Nanyuan Community Health Service Center of Fengtai District, Beijing, P.R. China
| | - Shuang Li
- Nanyuan Community Health Service Center of Fengtai District, Beijing, P.R. China
| | - Jing Han
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Quanri Liu
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Lingli Feng
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Chao Wang
- School of Public Health, Capital Medical University, Beijing, P.R.China
| | - Rong Xiao
- School of Public Health, Capital Medical University, Beijing, P.R.China
- Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, P.R. China
- * E-mail:
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Null genotypes of GSTM1 and GSTT1 and endometriosis risk: a meta-analysis of 25 case-control studies. PLoS One 2014; 9:e106761. [PMID: 25208225 PMCID: PMC4160205 DOI: 10.1371/journal.pone.0106761] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 08/10/2014] [Indexed: 12/20/2022] Open
Abstract
Endometriosis is one of the most frequent benign gynecological disorders. Numerous studies have shown an association between GSTM1 and/or GSTT1 polymorphisms and endometriosis susceptibility. However, these associations remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all existing studies and then performed a meta-analysis. Electronic literature searches of the PubMed, Chinese Biomedical, and China National Knowledge Infrastructure databases were performed up to December 2013. GSTM1-, GSTT1-, and dual-null genotypes were analyzed independently, and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated by comparing the null genotype with other genotypes using the random-effects or fixed-effects model. Twenty-five and 16 independent studies on GSTM1 and GSTT1 polymorphisms, respectively, and five GSTM1-GSTT1 interaction analyses were identified and included in this meta-analysis. Both GSTM1- and GSTT1-null genotypes increased risk of endometriosis (OR = 1.54, 95% CI: 1.30-1.83, P<0.001; OR = 1.41, 95% CI: 1.10-1.82, P = 0.007; respectively). Moreover, we found a significant positive association between the dual null genotype GSTM1-GSTT1 and endometriosis susceptibility (OR = 1.33, 95% CI: 1.03-1.72, P = 0.027). This meta-analysis provides evidence that null genotypes of GSTM1 and/or GSTT1 contribute to risk of endometriosis. Further investigations are required to confirm these findings.
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Shiba HF, El-Ghamrawy MK, Shaheen IAEM, Ali RAEG, Mousa SM. Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian pediatric patients with sickle cell disease. Pediatr Dev Pathol 2014; 17:265-70. [PMID: 24840051 DOI: 10.2350/14-03-1452-oa.1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
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.
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Affiliation(s)
- Hala Fathy Shiba
- 1 Clinical Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt
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Kan HP, Wu FL, Guo WB, Wang YZ, Li JP, Huang YQ, Li SG, Liu JP. Null genotypes of GSTM1 and GSTT1 contribute to male factor infertility risk: a meta-analysis. Fertil Steril 2013; 99:690-6. [DOI: 10.1016/j.fertnstert.2012.10.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2012] [Revised: 10/18/2012] [Accepted: 10/21/2012] [Indexed: 10/27/2022]
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Martínez-Ramírez OC, Pérez-Morales R, Castro C, Flores-Díaz A, Soto-Cruz KE, Astorga-Ramos A, Gonsebatt ME, Casas L, Valdés-Flores M, Rubio J. Polymorphisms of catechol estrogens metabolism pathway genes and breast cancer risk in Mexican women. Breast 2012; 22:335-43. [PMID: 23000097 DOI: 10.1016/j.breast.2012.08.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 08/07/2012] [Accepted: 08/20/2012] [Indexed: 12/17/2022] Open
Abstract
Breast cancer is associated to estrogen exposure. Allelic variants involved in estrogen metabolism might change the risk of developing this neoplasia. We examined the potential association of breast cancer risk in Mexican women with the polymorphisms CYP1A1 rs1048943, CYP1B1 rs1056836, COMT rs4680, GSTP1 rs1695, GSTT1 null and GSTM1 null which are involved in estrogen metabolism pathway. This study included 150 cases and 150 controls. A significant association was observed between, CYP1A1 rs1048943 (OR = 1.95, C.I. 1.13-3.36) and GSTP1 rs1695 (OR = 2.39, C.I. 1.24-4.24) polymorphisms with the risk of breast cancer. This risk was increased when the women were stratified according to their menopausal status. The results show that breast cancer risk significantly increases in women with 3-6 risk polymorphisms (OR = 3.75, C.I. 1.44-9.74).
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Affiliation(s)
- O C Martínez-Ramírez
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F., Mexico
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Kurose K, Sugiyama E, Saito Y. Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development. Drug Metab Pharmacokinet 2011; 27:9-54. [PMID: 22123129 DOI: 10.2133/dmpk.dmpk-11-rv-111] [Citation(s) in RCA: 184] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Drug lag, recently discussed extensively in Japan, can be divided into two phases: clinical development time and application review time. The former factor is still an important problem that might be improved by promoting multi-regional clinical trials and considering the results from other similar populations with Japanese, such as Koreans and Chinese. In this review, we compare the allelic or genotype frequencies of 30 relatively common functional alleles mainly between Eastern Asians and Europeans as well as among 3 major populations in Eastern Asian countries, Japan, Korea, and China, in 12 pharmacokinetics (PK)/pharmacodynamics (PD)-related genes; CYP2C9 (*2 and *3), CYP2C19 (*2, *3 and *17), 13 CYP2D6 haplotypes including *4, *5 and *10, CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5, *6 and *7), GSTM1 and GSTT1 null genotypes, SLCO1B1 521T>C, ABCG2 421C>A, and HLA-A*31:01 and HLA-B*58:01. In this review, differences in allele frequencies (AFs) or genotype frequencies (GFs) less than 0.1 (in the cases of highest AF (GF) ≥0.1) or less than 0.05 (in the cases of lowest AF (GF) <0.1) were regarded as similar. Between Eastern Asians and Europeans, AFs (or GFs) are regarded as being different for many alleles such as CYP2C9 (*2), CYP2C19 (*2, *3 and *17), CYP2D6 (*4 and *10), CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5*7), GSTT1 null and ABCG2 421C>A. Among the 3 Eastern Asian populations, however, only AFs of CYP2C19*3, CYP2D6*10, HLA-A*31:01 and HLA-B*58:01 are regarded as dissimilar. For CYP2C19*3, the total functional impact on CYP2C19 could be small if the frequencies of the two null alleles CYP2C19*2 and *3 are combined. Regarding CYP2D6*10, frequency difference over 0.1 is observed only between Japanese and Chinese (0.147). Although environmental factors should be considered for PK/PD differences, we could propose that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms. On the other hand, AFs of the two HLA alleles important for cutaneous adverse drug reactions are diverse even among Eastern Asians and thus should be taken into account.
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Affiliation(s)
- Kouichi Kurose
- Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan
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The role of glutathione S-transferase M1 and T1 gene polymorphisms and fruit and vegetable consumption in antioxidant parameters in healthy subjects. Br J Nutr 2011; 107:928-33. [DOI: 10.1017/s0007114511003746] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
The correlation of glutathione S-transferase (GST) M1/T1 genetic polymorphisms with oxidative stress-related chronic diseases was proved recently. The aim of the present study was to investigate the association of GSTM1/T1 genetic polymorphisms with antioxidant biomarkers and consumption of fruits and vegetables (F&V) in healthy subjects. In this study, for conducting a 3 d dietary survey, 190 healthy adults were recruited. After DNA extraction, a multiple PCR method was used for GSTM1/T1 genotyping. A spectrophotometer method was applied for the determination of plasma total antioxidant capacity (T-AOC), vitamin C level and erythrocyte GST enzyme activity. A general linear model was used to compare the mean values of antioxidant parameters for different GSTM1/T1 genotypes and consumption of F&V. Polymorphisms of GSTM1/T1 had no effects on plasma T-AOC and vitamin C levels. Deletion of the GSTM1 gene decreased the erythrocyte GST activity. There was correlation between plasma T-AOC and consumption of F&V in the GSTM1− or GSTT1+ subjects. A similar pattern was evident for erythrocyte GST activity in the GSTM1− subjects. No association was found among consumption of F&V and GSTM1/T1 genotypes and plasma vitamin C level. Different consumption of F&V had no impact on plasma T-AOC and vitamin C levels in the GSTM1−/GSTT1+ or GSTM1−/GSTT1− subjects. The erythrocyte GST activity was more sensitive to consumption of F&V in the individuals with the GSTM1−/GSTT1+ genotype. Association was found among GSTM1/T1 genotypes, antioxidant parameters and consumption of F&V. Large-scale and multiple ethnic studies are needed to further evaluate the relationship.
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Wu QF, Xing JP, Tang KF, Xue W, Liu M, Sun JH, Wang XY, Jin XJ. Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China. Asian J Androl 2008; 10:266-70. [DOI: 10.1111/j.1745-7262.2008.00347.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Mak JCW, Ho SP, Leung HCM, Cheung AHK, Law BKW, So LKY, Chan JWM, Chau CH, Lam WK, Ip MSM, Chan-Yeung M. Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics. Clin Exp Allergy 2007; 37:1150-7. [PMID: 17651144 DOI: 10.1111/j.1365-2222.2007.02704.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Asthma is a disease associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported. OBJECTIVE To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults. METHODS An age- and smoking status-matched case-control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR-RFLP). Plasma GST activity was measured by fluorometric assay. RESULTS The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34-0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001). CONCLUSION Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.
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Affiliation(s)
- J C W Mak
- Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Hong Kong, China
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Zhong S, Huang M, Yang X, Liang L, Wang Y, Romkes M, Duan W, Chan E, Zhou SF. Relationship of glutathione S-transferase genotypes with side-effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus. Br J Clin Pharmacol 2007; 62:457-72. [PMID: 16995867 PMCID: PMC1885164 DOI: 10.1111/j.1365-2125.2006.02690.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
AIMS Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE. METHODS DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile-->Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay. RESULTS Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients. CONCLUSIONS The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.
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Affiliation(s)
- Shilong Zhong
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou 510080, China
| | - Min Huang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou 510080, China
| | - Xiuyan Yang
- Department of Rheumatology & Clinical Immunology, the First Affiliated Hospital, Sun Yat-sen UniversityGuangzhou 510080 China
| | - Liuqin Liang
- Department of Rheumatology & Clinical Immunology, the First Affiliated Hospital, Sun Yat-sen UniversityGuangzhou 510080 China
| | - Yixi Wang
- Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen UniversityGuangzhou 510080, China
| | - Marjorie Romkes
- Center for Clinical Pharmacology, School of Medicine, University of PittsburghPittsburgh 15219, USA
| | - Wei Duan
- Department of Biochemistry, Faculty of Medicine, National University of SingaporeSingapore
| | - Eli Chan
- Deparment of Pharmacy, Faculty of Science, National University of SingaporeSingapore
| | - Shu-Feng Zhou
- Deparment of Pharmacy, Faculty of Science, National University of SingaporeSingapore
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Lin GF, Du H, Chen JG, Lu HC, Kai JX, Zhou YS, Guo WC, Zhang XJ, Lu DR, Golka K, Shen JH. Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China. Arch Toxicol 2007; 81:545-51. [PMID: 17318627 DOI: 10.1007/s00204-007-0187-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2006] [Accepted: 01/24/2007] [Indexed: 10/23/2022]
Abstract
A total of 2,402 cases of arsenic-related skin lesions (as of 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high arsenic coal. A significant difference of skin lesion prevalence was observed between two clans of different ethnicities (Hmong and Han) in one of the hyperendemic villages in this prefecture. This study was focused on a possible involvement of GST T1 and M1 polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. GST T1 and M1 polymorphisms were genotyped by an allele-specific PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analyzed. No significant deviations in the population frequencies of GST T1 and M1 0/0 genotypes or their combination were recorded between diagnosed skin lesion patients and asymptomatic individuals in both clans. Significantly higher As contents in hair and urine were observed in GSTM1 0/0 carriers, not in GSTT1 0/0 carriers. After stratified by ethnicity and gender, a statistically significant association of the GSTM1 0/0 genotype and higher As content in hair was only confirmed in the subgroups of ethnic Han clan members and all male villagers, not in ethnic Hmong clan members or in females. GST T1 and M1 homozygous deletions were not associated with an increased susceptibility to skin lesions in long-term exposure to indoor combustion of high As coal. The polymorphic status at the locus of GSTM1 might modulate individual's body burden of total As in some Chinese ethnic groups.
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Affiliation(s)
- Guo-Fang Lin
- Shanghai Institutes for Biological Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai, 200032, China
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Lu XM, Yang T, Xu SY, Wen H, Wang X, Ren ZH, Zhang Y, Wang W. Glutathione-S-transferase M1 polymorphisms on the susceptibility to esophageal cancer among three Chinese minorities: Kazakh, Tajik and Uygur. World J Gastroenterol 2006; 12:7758-61. [PMID: 17203516 PMCID: PMC4087538 DOI: 10.3748/wjg.v12.i48.7758] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the glutathione-S-transferase M1 (GSTM1) polymorphisms in three Chinese minorities, Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.
METHODS: A total of 1121 blood samples (442 males and 679 females) were obtained from healthy Kazakh (654), Uygur (412) and Tajik (55). Primary esophageal squamous cell cancer (ESCC) tissues from Kazakh were obtained from 116 patients who underwent surgery. GSTM1 polymorphisms were analyzed by a combined approach of PCR and electrophoresis techniques.
RESULTS: GSTM1 null genotype was found in 62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of GSTM1 null genotype in Uygur was observed compared with Kazakh (OR: 1.859, 95% CI: 1.445 -2.391, χ2 = 23.71, P = 0.000). In addition, GSTM1 null genotype was found in 23.53% of well-differentiated ESCC in Kazakh, in 49.23% of poorly differentiated ESCC, with a significant difference (OR: 3.152, 95% CI: 1.403-7.080, χ2 = 8.018, P = 0.007).
CONCLUSION: There is a marked difference in the frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null genotype is associated with differentiation of ESCC in Kazakh.
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Affiliation(s)
- Xiao-Mei Lu
- Medical Research Center, 1st Teaching Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
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Saadat M. No significant difference between Uygur and Han Chinese populations for genetic polymorphism of GSTP1. Clin Chim Acta 2006; 370:203. [PMID: 16814272 DOI: 10.1016/j.cca.2006.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2006] [Accepted: 02/07/2006] [Indexed: 10/25/2022]
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