• Title/Summary/Keyword: glutathione S-transferase polymorphisms

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GENETIC POLYMORPHISMS OF THE GLUTATHIONE S-TRANSFERASE AND CYP1A1 GENES IN KOREAN ORAL SQUAMOUS CELL CARCINOMA (한국인 구강 편평세포암에서 Glutathione S-transferase와 CYP1A1 유전자의 다형성)

  • Cha, In-Ho;Kwon, Jong-Jin;Park, Kwang-Kyun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.28 no.5
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    • pp.364-371
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    • 2002
  • Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.

Study on the Relationship between Polymorphisms in Glutathione S-transferase and Ischemic Cerebrovascular Disease

  • Han Sang-Hyuk;Park Sae-Wook;Shin Yong-Il;Cho Kwang-Ho;Moon Byung-Soon
    • The Journal of Korean Medicine
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    • v.25 no.4
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    • pp.36-42
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    • 2004
  • Objective : Glutathione S-transferase polymorphism (GST) were examined in 120 cases with ischemic cerebrovascular disease (ICVD) to test the hyperthesis that GST polymorphisms confer a risk to an individual to develop ICVD. Tobacco smoking is a major cause of both cancer and vascular disease. Methods : therefore We were stratified the subjects with ICVD for smoking status, and then examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of ICVD Results : Neither GSTM1 nor GSTT1 genotypes in the ICVD group was significantly different from the control group (n=207), even in smokers. We attempted the combined analyses for GSTM1 and GSTT1 genotypes in ICVD for smoking status. No significant association observed between the combined genotypes and ICVD Conclusion : Our observation do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for ICVD, even in smokers.

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Association between the Polymorphism of Glutathione S-transferase Genes and Chronic Myeloid Leukemia in Asian Population: a Meta-analysis (아시아인종에서 만성골수성백혈병과 Glutathione S-transferase 유전자 다형성의 메타분석)

  • Kim, Hee Sung
    • The Journal of the Korea Contents Association
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    • v.17 no.10
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    • pp.289-299
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    • 2017
  • To verify the association between susceptibility to chronic myeloid leukemia (CML) and GSTM1, GSTT1 gene polymorphisms in Asian populations, 9 papers published until July 2017 were cited in a meta-analysis. The null present types of the GSTM1, GSTT1 gene were analyzed individually. The significant association was found between CML and GST polymorphism (GSTM1; OR=1.306, 95% CI=1.091-1.563, p=0.004, GSTT1; OR=1.987, 95% CI=1.438-2.746, p=0.000). In addition, there was association between CML and the null type of the combination GSTM1-GSTT1 polymorphisms (OR=4.191, 95% CI=2.833-6.201, p=0.000). Thus, genetic polymorphisms of the GSTM1, GSTT1 and combination GSTM1-GSTT1 polymorphism in Asian populations may be risk factors for CML.

Interrelationships among Glutathione S-Transferase Polymorphisms, Cerebrovascular Disease and Sasang Constitution (글루타티온 S-전환효소 다형성과 뇌혈관질환(腦血管疾患) 및 사상체질 사이의 연관성(聯關性)에 관한 연구)

  • Kim, Jong-Kwan;Han, Byung-Sam;Kim, Kyung-Yo;Go, Gi-Deok;Ok, Yoon-Young
    • Journal of Sasang Constitutional Medicine
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    • v.14 no.1
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    • pp.123-131
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    • 2002
  • Glutathione S-transferase polymorphisms (GST) were examined in 98 cases with cerebrovascular disease (CVD) to test the hypothesis that GST polymorphisms confer a risk to an individual to develop CVD. Tobacco smoke is a major cause of both cancer and vascular disease. We therefore were stratified the subjects with CVD for smoking status, and then examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of CVD. Neither GSTM1 nor GSTT1 genotypes in the CVD group was significantly different from the control group (n=230), even in smokers. We attempted the combined analyses for GSTM1 and GSTT1 genotypes in CVD for smoking status. No significant association observed between the combined genotypes and CVD. We also classified the subjects and control group into four types according to Sasang Constitutional Medicine, Korean Traditional Oriental Medicine, and investigated the association among GST genotypes, CVD, and Sasang constitutional classification. Our observations do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for CVD, even in smokers. Furthermore, we first attempted to evaluate the efficacy of Sasang Constitutional Medicine, and to find an association with CVD.

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Effects of the Genetic Polymorphisms on Urinary Excretion of 1-Hydroxypyrene and 2-Naphthol (일반인구에서 유전자 다형성이 요중 1-hydroxypyrene 및 2-naphthol의 배설량에 미치는 영향)

  • Hwang Moon-Young;Cho Byung-Mann;Moon Seong-Bae
    • Journal of Environmental Science International
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    • v.14 no.5
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    • pp.499-511
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    • 2005
  • This study was performed to determine the effects of genetic polymorphisms, such as glutathione S-transferase ${\mu}1(GSTM1)$, glutathione S-transferase ${\Theta}1\;(GSTM1)$, glutathione S-transferase ${\pi}l (GSTP1)$, aryl hydrocarbon N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1) on the concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol in general population with no occupational exposure to polycyclic aromatic hydrocarbons (PAHs). Study subjects were 257 men who visited a health promotion center in Susan. A questionnaire was used to obtain detailed data about age, smoking, drinking, body fat mass, intake of fat etc. Urinary l-OHP and 2-naphthol concentration were analyzed by HPLC system with a fluorescence detector. A multiplex PCR method was used to identify the genotypes for GSTM1 and GSTT1. The polymorphisms of GSTP1, NAT2, CYP1A1 and CYP2E1 were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Urinary 1-OHP concentration was higher in deleted genotype of GSTM1, increased as smoking and alcohol drinking increased. Urinary 2-naphthol concentration was also rely on the age and smoking. Neither genetic polymorphism nor drinking-related factors were significantly related to urinary 2-naphthol concentration. No significant relation was found between physical characteristics and concentrations of urinary PAHs metabolites in the subjects, but the geometric mean of urinary 1-OHP and 2-naphthol was higher in the group with higher value compared to median value. These data suggest that in general population occupationally not exposed to PAHs, urinary concentration of PAHs metabolites is influenced by smoking, alcohol drinking and deleted genotype of GSTM1 in 1-OHP and smoking in 2-naphthol.

Glutathione S-transferase polymorphisms and traditional classification in Korean population with cerebrovascular disease

  • Um, Jae-Young;Ok, Yoon-Young;Joo, Jong-Cheon;Kim, Kyung-Yo;Kim, Na-Hyung;Hong, Seung-Heon;Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.4 no.2
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    • pp.112-119
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    • 2004
  • Glutathione S-transferase polymorphisms (GST) were examined in 98 cases with cerebrovascular disease (CVD) to test the hypothesis that GST polymorphisms confer a risk to an individual to develop CVD. Tobacco smoke is a major cause of both cancer and vascular disease. We therefore were stratified the subjects with CVD for smoking status, and then examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of CVD. Neither GSTM1 nor GSTT1 genotypes in the CVD group was significantly different from the control group (n=230), even in smokers. We attempted the combined analyses for GSTM1 and GSTT1 genotypes in CVD for smoking status. No significant association observed between the combined genotypes and CVD. We also classified the subjects and control group into four types according to Sasang Constitutional Medicine, Korean Traditional Oriental Medicine, and investigated the association among GST genotypes, CVD, and Sasang constitutional classification. Our observations do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for CVD, even in smokers. Furthermore, we first attempted to evaluate the efficacy of Sasang Constitutional Medicine, and to find an association with CVD.

Glutathione S-Transferase T1 and M1 Polymorphisms and Risk of Uterine Cervical Lesions in Women from Central Serbia

  • Stosic, Ivana;Grujicic, Darko;Arsenijevic, Slobodan;Brkic, Marija;Milosevic-Djordjevic, Olivera
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3201-3205
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    • 2014
  • The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions.

Glutathione-S-Transferase Polymorphisms (GSTM1, GSTT1 and GSTP1) and Acute Leukemia Risk in Asians: a Meta-analysis

  • Tang, Zhen-Hai;Zhang, Chi;Cheng, Pan;Sun, Hong-Min;Jin, Yu;Chen, Yuan-Jing;Huang, Fen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2075-2081
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    • 2014
  • The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and risk of acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the precise association in 23 studies identified by a search of PubMed and several other databases, up to December 2013. Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publication bias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 but not GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01, 95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1 null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors for acute leukemia. Further well-designed studies are needed to confirm our findings.

Antioxidative Status, DNA Damage and Lipid Profiles in Korean Young Adults by Glutathione S-Transferase Polymorphisms (Glutathione S-transferase (GST) 유전자 다형성에 따른 우리나라 젊은 성인의 항산화 상태, DNA 손상 및 지질 양상)

  • Jo, Hye-Ryun;Lee, Hye-Jin;Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.44 no.1
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    • pp.16-28
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    • 2011
  • Oxidative stress leads to the induction of cellular oxidative damage, which may cause adverse modifications of DNA, proteins, and lipids. The production of reactive species during oxidative stress contributes to the pathogenesis of many diseases. Antioxidant defenses can neutralize reactive oxygen species and protect against oxidative damage. The aim of this study was to assess the antioxidant status and the degree of DNA damage in Korean young adults using glutathione s-transferase (GST) polymorphisms. The GSTM1 and GSTT1 genotypes were characterized in 245 healthy young adults by smoking status, and their oxidative DNA damage in lymphocytes and antioxidant status were assessed by GST genotype. General characteristics were investigated by simple questionnaire. From the blood of the subjects, GST genotypes; degree of DNA damage in lymphocytes; the erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase; plasma concentrations of total peroxyl radical-trapping potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene and cryptoxanthin, as well as plasma lipid profiles, conjugated diene (CD), GOT, and GPT were analyzed. Of the 245 subjects studied, 23.2% were GSTM1 wild genotypes and 33.4% were GSTT1 wild genotype. No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and the plasma TRAP level, CD, GOT, and GPT levels were observed between smokers and non-smokers categorized by GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}$- and ${\gamma}$-tocopherol increased significantly in smokers with the GSTT1 wild genotype (p < 0.05); however, plasma level of ${\alpha}$-carotene decreased significantly in non-smokers with the GSTM1 wild genotype (p < 0.05). DNA damage assessed by the Comet assay was significantly higher in non-smokers with the GSTM1 genotype; whereas DNA damage was significantly lower in non-smokers with the GSTT1 genotype. Total cholesterol and LDL cholesterol levels were significantly higher in non-smokers with the GSTT1 genotype than those with the GSTT1 wild genotype (p < 0.05). In conclusion, the GSTM1 genotype or the GSTT1 wild genotype in non-smokers aggravated their antioxidant status through DNA damage of lymphocytes; however, the GSTT1 wild type in non-smokers had normal plasma total cholesterol and LDL-cholesterol levels. This finding confirms that GST polymorphisms could be an important determinant of antioxidant status and plasma lipid profiles in non-smoking young adults. Further study is necessary to clarify the antioxidant status and/or lipid profiles of smokers with the GST polymorphism and to conduct a study with significantly more subjects.