• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6375-6378
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• 2013

Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3861-3864
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• 2013

Glutathione S-transferase (GST) enzyme levels are associated with risk of many cancers, including hematologic tumours. We here aimed to investigate the relationships between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of AML. Genotyping of GSTs was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR-CTPP) method in 163 cases and 204 controls. Individuals carrying null GSTT1 genotype had a 1.64 fold risk of acute leukemia relative to a non-null genotype (P<0.05). A heavy risk was observed in those carrying combination of null genotypes of GSTM1 and GSTT1 and GSTP1 Val allele genotypes when compared with those carrying wild genotypes, with an OR (95% CI) of 3.39 (1.26-9.26) (P<0.05). These findings indicate that genetic variants of GST and especially the GSTT1 gene have a critical function in the development of AML. Our study offers important insights into the molecular etiology of AML.

• International Journal of Industrial Entomology and Biomaterials
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• 제10권1호
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• pp.51-59
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• 2005

Genetic diversity within and between populations of Antheraea mylitta Drury was studied using thirty individuals from three ecoraces using 12 ISSR and 10 RAPD primers. Rally, Daba and Modal ecoraces were collected from Chattisgarh, Jharkhand and Orissa states of India respectively. The ISSR and RAPD primers generated $94.7\%$ and $95.6\%$ polymorphism among the 30 individuals. The cluster analysis grouped these individuals according to their ecorace. The intra-ecoracial heterozygosity estimated with ISSR markers were $0.123{\pm}0.18,\;0.169{\pm}0.17\;and\;0.214{\pm}0.17$ respectively for Modal, Raily and Daba ecoraces. Like wise, with RAPD markers the intraecoracial heterozygosity was $0.17{\pm}0.22$ in Modal, $0.229{\pm}0.17$ in Raily and $0.23{\pm}0.19$ in Daba ecoraces. However, the significantly low genetic differentiation (GST) (0.182 for ISSR and 0.161 for RAPD) and the high gene flow (Nm) (2.249 for ISSR and 2.60 for RAPD markers) among the ecoraces revealed that the amount of genetic diversity present among the ecoraces is not significant enough to make drastic genetic drifts among these ecoraces in the near future.

• 대한두경부종양학회지
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• 제18권2호
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• pp.150-156
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• 2002

Objectives: Most of human cancers may result from exposure to environmental carcinogens, and individual effectiveness in the detoxification of these chemicals will influence susceptibility to malignant disease. Glutathione S-Transferases(GSTs) enzymes are involved in the detoxification of active metabolites of many carcinogens from tobacco smoke and may be important in modulating susceptibility to smoke-related cancer. The purpose of this study is to determine the polymorphism of GSTM1, GSTT1, and GSTP1 in control group and head and neck squamous cell carcinoma group of Korean, and to investigate the effect of GSTs polymorphism on the risk of head and neck cancer. Materials and Methods: A hospital-based case-control study was performed with a group of 133 control individual and 136 head and neck squamous cell carcinoma patients. The polymorphisms of GSTs were analysed using polymerase chain reaction in GSTM1 and GSTTl, and polymerase chain reaction-restriction fragment length polymorphism in GSTP1. Results: The relative risk (odds ratio) of GSTM(-) genotype was 1.14(95% CI, 0.70-1.85) compared to GSTM1(+). The odds ratio of GSTTl(-) genotype was 0.91(95% CI, 0.55-1.50). In old age($65$) group, the odds ratio of GSTT1(-) genotype was 5.2(95% CI, 1.53-17.89). The GSTP1 Val/Val genotype conferred a 1.7-fold risk(95% CI, 0.40-7.34) of head and neck cancer compared with GSTP1 Ile/Ile genotype. Among the combined genotypes of GSTs, GSTM1(-)/GSTT1(+)/GSTP1 Val/Val and GSTM1(-)/GSTTl(-)/GSTP1 Ile/Val genotypes conferred a 2.6-fold and 1.3-fold risk(95% CI, 0.24-14.15 and 0.43-3.14) compared with the GSTM1(+)/GSTTl(+)/GSTP1 Ile/Ile genotype, respectively. Conclusion: Polymorphism of GSTs might modulate susceptibility to head and neck cancer in Korean population. The genotype of GSTP1 Val/Val and combined genotypes of GSTM1(-)/GSTT1(+)/GSTP1 Val/Val, and GSTM1(-)/GSTT1(-)/GSTP1 Ile/Val might be important risk factors to determine the individual susceptibility to head and neck squamous cell carcinoma.

• Journal of Nutrition and Health
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• 제48권6호
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• pp.468-475
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• 2015

우리나라 일부 건강한 유아를 대상으로 Mn-SOD Val16Ala, GSTP1 Ile105Val, GSTT1 present/null, GSTM1 present/null 유전자 다형성 분포를 살펴본 결과, Mn-SOD Val/Val형, GSTP1 Ile/Ile형, GSTT1 null 형, GSTM1 null 형이 주된 (major) 유전자형인 것으로 나타났다. 이 중 Mn-SOD Val/Val형은 Val/Ala 또는 Ala/Ala형에 비해 소변 8-OHdG 수준이 유의적이지는 않으나 높은 경향을 나타내었고, GSTP1 Ile/Ile형은 Ile/Val 또는 Val/Val형에 비해 소변 8-OHdG 수준이 유의적으로 낮았다. 간접흡연에의 노출 여부와 간접흡연-유전자 다형성의 상호 작용이 산화손상지표에는 유의적인 영향을 미치지 않는 것으로 나타났다. 이상의 결과로 볼 때 건강한 유아에서 GSTP1 Val allele 보유한 경우 산화적 손상에 대해 취약할 수 있음을 제시하며, 추후 대규모 연구를 통한 검증 및 이들 유전자형을 보유한 대상자를 위한 효과적인 영양 중재방안에 대한 고려가 필요할 것으로 사료된다.

• Nutrition Research and Practice
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• 제9권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.157-163
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• 2012

Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using ${\chi}^2$-based Q statistic and the $I^2$ statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.29-34
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• 2006

Immunoglobulin E (IgE) plays an important role in the development of allergic disorders including asthma. Cigarette smoking was reported to elevate serum IgE level and air pollutants such as $NO_{2}$ have been reported to modulate the immune system including inflammation. Moreover, genetic polymorphisms of glutathione S-transferases (GSTs) were reported to affect inflammatory diseases including asthma. Therefore, in the present study we tried to investigate whether tobacco smoke or $NO_{2}$ exposure increases the level of IgE and the GST gene polymorphisms are associated with change of IgE level due to tobacco smoke or $NO_{2}$ exposure. We measured urinary cotinine, personal $NO_{2}$ exposure, and serum IgE levels in 300 healthy university students without allergic disorders. Allelic loss of the GSTM1 and GSTT1 and the GSTP1 (lle105Val) polymorphism were determined by PCR and RFLP. Total serum IgE levels were significantly different according to urinary cotinine levels (P=0.046), while $NO_{2}$ passive dosimeter level and genetic polymorphisms of three GSTs were not associated with total IgE level. Moreover, subjects with cotinine $500\;{\mu}g/g$ creatinine or more showed the highest level of total IgE when they had null type of GSTM1, null type of GSTT1, or variant type of GSTP1 (P<0.05). When we considered IgE level according to urinary cotinine levels in strata with the combinations of GSTM1, GSTT1, and GSTP1 genetic polymorphisms, the subjects with GSTM1 null, GSTT1 null, and GSTP1 variant types showed the largest difference between IgE levels of subpopulations according to cotinine levels (P=0.030). However, there was no significant difference between IgE levels of subpopulations according to $NO_{2}$ passive dosimeter levels in any group with combinations of GSTM1, GSTT1, and GSTP1 polymorphisms. This result suggests that smoking increases allergic response measured as IgE level and combinations of the GSTM1, GSTT1, and GSTP1 polymorph isms modify the effect of smoking on serum IgE level.

• Journal of Nutrition and Health
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• 제50권1호
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• pp.10-24
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• 2017

본 연구는 건강한 성인 남녀를 대상으로 glutathione S-transferase (GST)M1 및 T1 유전자 다형성에 따라 한식에서 주로 섭취하는 식물성 식품군과 한식 식단의 DNA 손상 감소효과를 측정하여 유전적 민감도가 어떻게 나타나는지를 알아보기 위해 수행되었다. 이를 위하여 건강한 성인 남녀 59명을 대상으로 혈액을 채취하여 GST genotype을 분류하였으며 그 중 17명을 선발하여 DNA 손상 감소효과를 Comet assay를 이용하여 측정하였고 DNA damage relative score로 나타냈다. 제 5기 2차년도 국민건강영양조사를 활용하여 한국인이 많이 섭취하는 식물성 식품을 10가지 식품군 (감자류, 견과류, 곡류, 과일류, 김치류, 두류, 버섯류, 오일류 채소류 해조류)으로 분류 후, 각 식품군별 총 섭취량의 1% 이상을 섭취한 84종의 식품을 한식 식물성 식품으로 최종 선정하였으며 한식 식단 (Korean diet)은 한국영양학회에서 발행한 [2010 한국인 영양섭취 기준]에 제시되어 있는 1주일 표준식단 (2,000 kcal/day)을 사용하였다. GSTM1 유전자 다형성에 따른 한식 식물성 식품군의 Tail moment로 본 DNA 손상 감소효과는 곡류와 오일류에서만 GSTM1 wild type보다 mutant type에서 유의하게 높았다. 이에 비해 DNA 손상 감소 효과를 % DNA in tail과 Tail moment로 본 결과, 견과류 과일류 채소류 버섯류 김치류 해조류에서 GSTT1 mutant type에 비해 wild type에서 유의하게 더 높게 나타났다. GSTM1과 GSTT1의 combined genotype에 따라 한식 식물성 식품의 DNA 손상 감소효과를 본 결과, 과일류, 김치류, 버섯류, 채소류, 해조류는 1군 (GSTM1+/GSTT1+) 및 3군 (GSTM1-/GSTT1+)에서, 오일류는 3군 (GSTM1-/GSTT1+)에서 DNA 손상 감소 효과가 유의하게 높았으며. 감자류, 견과류, 곡류, 두류, Total은 DNA 손상 감소 효과가 2군 (GSTM1+/GSTT1-) 및 3군 (GSTM1-/GSTT1+)에서 유의하게 높아 식품군에 따라 GST 유전자 다형성에 따른 DNA 손상 감소효과가 다르게 나타나는 것을 확인할 수 있었다. 한식 식단은 DNA 손상의 세 가지 지표인 % DNA in tail, Tail moment, Tail length로 측정해본 결과 GSTM1의 경우 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1의 경우는 genotype에 따라 DNA 손상이 달라지는 경향은 있었지만 유의한 차이를 나타내지 않았다. 결론적으로 한식에서 주로 섭취하는 식물성 식품군에서는 식품에 따라 부분적으로 GSTM1은 mutant type에서, GSTT1은 wild type에서 DNA 손상 보호효과가 더 크게 나타났으며, GSTM1과 GSTT1의 combined genotype에 따른 DNA 손상 보호효과는 식품군에 따라 다르게 나타났다. 반면, 한식 식단에서는 DNA 손상 보호효과가 GSTM1 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1 genotype에는 영향을 받지 않는 것으로 나타났다. 이와 같은 결과는 한식 식물성 식품군 및 식사패턴의 항산화 기능 우수성을 증명하는 기초자료가 될 것이며, 나아가 개인별 유전자에 따른 항산화 맞춤영양연구를 시작하는 시발점이 될 수 있을 것이다. 앞으로 GST 유전자 다형성에 따른 한식과 한식 식물성 식품군의 유전적 민감도를 더 명확하게 규명하기 위해서는 대상 인원을 늘려 수행하는 광범위한 연구가 필요할 것으로 보인다.

• 한국환경보건학회지
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• 제47권6호
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• pp.530-539
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• 2021

Background: In South Korea, areas around abandoned metal mines are designated as regions with high arsenic (As) contamination. However, studies assessing urinary As exposure, As metabolism, and relevant genetic polymorphisms in residents of these metal mine areas are lacking. Objectives: To identify factors associated with As exposure and evaluate the effects of MTHFR, As3MT, and GSTO1 genetic polymorphisms on As metabolism in residents of abandoned metal mine areas by measuring urinary As species. Methods: Urinary As species (arsenite [As³⁺], arsenate [As⁵⁺], monomethyl arsonic acid, and dimethylarsinic acid) were isolated using high-performance liquid chromatography in combination with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Four genetic polymorphisms (MTHFR A222V, MTHFR E429A, GSTO1 A140D, As3MT M287T) were analyzed in 144 residents of four areas around abandoned metal mines. Results: The study sample was comprised of 34.7% men and 65.3% women, with a mean age of 70.7±10.9 years. The urinary inorganic As concentration was higher among those consuming more than half locally produced rice (0.31 ㎍/L) than those consuming less than half such rice (0.18 ㎍/L). The urinary dimethylarsinic acid concentration was higher in the group that had consumed seafood in the past day (31.68 ㎍/L) than in those who had not (22.37 ㎍/L). Furthermore, individuals heterozygous in the MTHFR A222V and GSTO1 A140D polymorphism had higher urinary arsenic species concentrations than did individuals with a wild type or homozygous for the variant allele. Conclusions: Consumption of locally produced rice was associated with inorganic As exposure, whereas seafood consumption was associated with organic As exposure among residents of abandoned metal mine areas. There was no clear association between MTHFR A222V and GSTO1 A140D polymorphisms and As metabolism.