• Title/Summary/Keyword: GST polymorphism

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Glutathione S-transferase polymorphism of neonatal hyperbilirubinemia in Korean neonates (한국인 신생아 황달과 Glutathione S-transferase 다형성에 관한 연구)

  • Kang, Chang Seok;Hong, Seung Su;Kim, Ji Sook;Kim, Eun Ryoung
    • Clinical and Experimental Pediatrics
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    • v.51 no.3
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    • pp.262-266
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    • 2008
  • Purpose : Glutathione S-transferase (GST) is a polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous diseases. Several allelic variants of GSTs show impaired enzyme activity and are suspected to increase the susceptibility to diseases. Bilirubin is bound efficiently by GST members. The most commonly expressed gene in the liver is GSTM1, and GSTT1 is expressed predominantly in the liver and kidneys. To ascertain the relationship between GST and neonatal hyperbilirubinemia, the distribution of the polymorphisms of GSTT1 and GSTM1 were investigated in this study. Methods : Genomic DNA was isolated from 88 patients and 186 healthy controls. The genotypes were analyzed by polymerase chain reaction (PCR). Results : The overall frequency of the GSTM1 null was lower in patients compared to controls (P=0.0187, Odds ratio (OR) =0.52, 95% confidence interval (CI), 0.31-0.88). Also, the GSTT1 null was lower in patients compared to controls (P=0.0014, OR=0.41, 95% CI=0.24-0.70). Moreover, the frequency of the null type of both, in the combination of GSTM1 and GSTT1, was significantly reduced in jaundiced patients (P=0.0008, OR=0.31, 95% CI=0.17-0.61). Conclusion : We hypothesized that GSTM1 and GSTT1 might be associated with neonatal hyperbilirubinemia. However, the GSTT1 and GSTM1 null type was reduced in patients. Therefore the null GSTT1, null GSTM1, and null type of both in the combination of GSTM1 and GSTT1 may be not a risk factor of neonatal jaundice.

GSTP1 Gene Ile105Val Polymorphism Causes an Elevated Risk for Bladder Carcinogenesis in Smokers

  • Pandith, Arshad Ahmad;Lateef, Adil;Shahnawaz, Sheikh;Hussain, Aashaq;Malla, Tahir Mohiuddin;Azad, Niyaz;Shehjar, Fahim;Salim, Mosin;Shah, Zafar Amin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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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.

Glutathione S-transferase T1, M1 and P1 Genetic Polymorphisms and Susceptibility to Colorectal Cancer in Turkey

  • Gorukmez, Ozlem;Yakut, Tahsin;Gorukmez, Orhan;Sag, Sebnem Ozemri;Topak, Ali;Sahinturk, Serdar;Kanat, Ozkan
    • 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.

Polymorphism of Glutathione S-Transferase(GST)M1, GSTT1, GSTP1 and Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma in Korean Population (한국인 두경부 편평세포암 환자에서 Glutathione S-transferase(GST)M1, GSTT1 및 GSTP1유전자 다형성 및 유전적 감수성)

  • Tae Kyung;Seo In-Seok;Kang Mee-Jeong;Cho Seok-Hyun;Kim Kyung-Rae;Lee Hyung-Seok
    • Korean Journal of Head & Neck Oncology
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    • v.18 no.2
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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.

Distribution of Glutathione S-Transferase Omega Gene Polymorphism with Different Stages of HBV Infection Including Hepatocellular Carcinoma in the Egyptian Population

  • Shaban, Nadia Z;Salem, Halima H;Elsadany, Mohamed A;Ali, Bahy A;Hassona, Ehab M;Mogahed, Fayed AK
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.2145-2150
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    • 2016
  • Background: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. Materials and Methods: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. Results: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. Conclusions: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

Risk Effects of GST Gene Polymorphisms in Patients with Acute Myeloid Leukemia: A Prospective Study

  • Zhou, Lei;Zhu, Yan-Yun;Zhang, Xiao-Dong;Li, Yang;Liu, Zhuo-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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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.

Genetic Diversity and Population Structure of maize, Zea mays, in Both Landraces and Cultivar Lines

  • Huh, Man-Kyu;Lee, In-Sup
    • Journal of Life Science
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    • v.12 no.1
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    • pp.27-32
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    • 2002
  • Enzyme electrophoresis was used to estimate genetic diversity and population structure of maize, Zea mays L. (Graminales) in Korea. In nine populations, fourteen of the 24 loci (58.3 %) showed detectable polymorphism. Genetic diversity (0.205) was higher than average values for species with similar life history traits. Although our data are relatively small and the landraces not direct ancestors of cultivar, apparently the domestication process has eroded the levels of genetic variation of maize. The recent cultivars were found to have fewer alleles per locus (1.42 vs. 1.56), fewer alleles per polymorphic locus (2.27 vs. 2.33), lower percent polymorphic locus (33.3% vs. 41.7%), and lower diversity (0.159 vs. 0.185) than landraces. These genetic diversity parameters indicated that the cultivar populations were genetically depauperate relative to landlaces. The GST value of nine populations was 0.239. Nearly 76% of the total genetic diversity in Zea mays was apportioned within populations. The indirect estimate of gene new based on mean GST was moderate (Nm=0.80).

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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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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.