• 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.

• 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.

• 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.

• 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.

• Sleep Medicine and Psychophysiology
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• v.22 no.1
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• pp.25-29
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• 2015

Objectives: The pathophysiology of restless legs syndrome (RLS) has not been fully elucidated. Oxidative stress might play a role in the development of RLS and other antipsychotic-induced side effects such as tardive dyskinesia. In the present study, we investigated whether the glutathione S-transferase (GST) gene polymorphisms are associated with antipsychotic-induced RLS in schizophrenia. Methods: We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. The GST-M1, GST-T1 and GST-P1 loci were analyzed using PCR-based methods. Results: We divided the subjects into 2 groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). There were no significant differences in the distributions of the GST-M1 genotypes (${\chi}^2=3.56$, p = 0.059), GST-T1 (${\chi}^2=0.51$, p = 0.476) and GST-P1 (${\chi}^2=0.57$, p = 0.821) between the 2 groups. Comparison of the RLS score among genotypes of the GST-M1 (t = -1.54, p = 0.125), GST-T1 (t = -0.02, p = 0.985) and GST-P1 (F = 0.58, p = 0.560) revealed no significant difference. Conclusion: These data suggest that GST gene polymorphisms do not confer increased susceptibility to RLS symptoms in schizophrenic patients. Future studies are necessary to evaluate the possible influences of other candidate genes involved in the reactive oxygen species system.

• 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.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.49-56
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• 2015

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS: 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS: Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS: These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes.

• Journal of Nutrition and Health
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• v.44 no.5
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• pp.366-377
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• 2011

Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, ${\beta}$-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1- or GSTT1-present genotype than those with the GSTM1-present or GSTT1- genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except ${\beta}$-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1- genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of ${\alpha}$-carotene, ${\beta}$-carotene, and cryptoxanthin. In conclusion, the GSTM1- and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1- or GSTT1-present genotypes might show significantly higher values than expected.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.65-70
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• 2004

Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3855-3859
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• 2016

Colorectal cancer (CRC) is reproted to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and disposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values p<0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey.