• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6263-6267
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• 2012

Background: Glutathione-S-transferase (GST) is an important phase II xenobiotic compound metabolizing enzyme family, involved in tolerance to a particular drug or susceptibility to a diseasec. This study focused the GSTM1 and T1 null allele frequency in the Gujarat population with a comparison across other Inter- and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Methods: DNA was isolated by a salting out method and GSTM1 and T1 homozygous null genotypes were detected by multiplex polymerase chain reaction in 504 unrelated individuals. The genotype distribution of null alleles was compared with Indian and non Indian ethnics reported earlier in the literature using Fisher's test. Results: The frequencies of the homozygous null genotypes of GSTM1 and GSTT1 were 20% (95%CI 16.7-23.9) and 35.5% (95%CI 31.4-39.9) respectively. GSTM1 null frequency did not deviate from most other Indian ethnic groups but differed from the majority of those of non Indian ethnicity studied. The frequency of homozygous null type of GSTT1 was significantly higher and deviated from all Indian groups and a few of non Indian ethnicity. Conclusions: Gujarat ethnicity, possibly the most susceptible for GSTT1 dependent drug disposition and diseases regarding effects of pollution. Further, the results have implications for GSTT1 dependent drugs used for treatment, a serious problem which needs to be solved by physicians and clinical researchers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3325-3328
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• 2012

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.355-361
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• 2015

Background: Deletion types of genetic variants of glutathione S-transferase (GST) M1 and T1, the GSTM1 null and GSTT1 null which are risk factors for certain cancers, have been ubiquitously found in human populations but their worldwide distribution pattern is unclear. Materials and Methods: To perform a meta-analysis, a systematic search for the literature on GSTM1 and GSTT1 null genotypes was done to identify 63 reports for 81 human populations. Relationships between the GSTM1 and GSTT1 null genotype frequencies and the absolute latitude of 81 populations were tested by Spearman's rank correlation coefficient. Results: A significant positive correlation was detected between the GSTM1 null genotype frequency and the absolute latitude (r=0.28, p-value <0.05), whereas the GSTT1 null genotype frequency and absolute latitude showed a significant negative correlation (r= -0.41 p-value <0.01). There was no correlation between the frequencies of GSTM1 and GSTT1 null genotype in each population (r= -0.029, p-value=0.80). Conclusions: Latitudinal clines of the distribution of the GSTM1 and GSTT1 null genotypes may be attributed to the result of gene-environmental adaptation. No functional compensation between GSTM1 and GSTT1 was suggested by the lack of correlation between the null frequencies for GSTM1 and GSTT1.

• Clinical and Experimental Pediatrics
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• 제51권3호
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• pp.262-266
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• 2008

목 적 : GSTs는 glutathione과 친전자성 화합물의 결합을 촉매하여 생체내에 독성 물질로부터 조직을 보호하는 효소로, 여러 다형성이 확인 되었으며 일부 GSTs의 null 유전자형을 가진 사람은 GSTs 단백을 생성하지 못하여 다양한 질병의 감수성에 영향을 미친다고 보고 되었다. 이것은 빌리루빈과 같은 non-substrate ligand와 결합하여 세포내로 운반하는 역할을 하는 대표적인 ligandin이며 빌리루빈을 간세포 내 소포체로 이동시켜 UGT를 통해 glucuronidation 시키는 역할을 한다. 이 연구에서는 빌리루빈 대사의 ligandin인 GSTs 중 GSTM1, GSTT1과 신생아 황달과 연관성이 있는 지 알아보고자 본 연구를 시행하였다. 방 법 : 혈청 빌리루빈 수치가 12 mg/dL 이상인 건강하고 위험인자가 없는 만삭아 중 신생아 고빌리루빈혈증 환아 88명, 대조군은 186명을 대상으로 혈액 0.5 cc를 채혈하여 DNA를 분류하였고 중합효소 연쇄 반응을 수행하여 DNA band를 확인하였다. 결 과 : 대조군의 GSTM1 null 유전형 58.1%, GSTT1의 null 유전형 53.2%였다. 환자군에서 GSTM1 null 유전형은 42% (P=0.0187), GSTT1 null 유전형은 31.8% (P=0.0014)로 통계학적 연관성이 있었다. GSTM1/GSTT1 null/null인 경우, 환자군에서 20명(22.7%)(P=0.0008), GSTM1/GSTT1 null/present인 경우 환자군에서 17명(19.3%) (P=0.0470), GSTM1/GSTT1 present/null인 경우 환자군에서 8명(9.1%) (P=0.0066)으로 나타났다 결 론 : GSTM1과 GSTT1 모두 환자군에서 null 유전형이 대조군에 비하여 더 적게 나타나 GSTs null 유전형이 신생아 고빌리루빈혈증의 위험인자는 아니었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5037-5042
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• 2012

Background: Tobacco contains agents which generate various potent DNA adducts that can cause gene mutations. Production of DNA adducts may be neutralized by glutathione S transferase (GST) along with other phase I and phase II enzyme systems. The existence of null type of GST among the population increases the susceptibility to various disorders and diseases. The present study focuses on the impact of high tobacco usage and possible null type mutation in GST loci. Methods: Genotypes of GST were detected by multiplex polymerase chain reaction in unrelated 504 volunteers of high tobacco using natives of Gujarat. Allelic frequencies were calculated using Statistical Package for Social Studies-16 software. Hardy Weinberg Equilibrium (HWE) was calculated using Chi square test. Two sided Fisher's significance test was used to compare allelic frequencies of different populations. Results: The frequency of homozygous null genotype of GSTM1 and GSTT1 were 20% (95% CI 16.7-23.9) and 35.5% (95% CI 31.4-39.9) respectively. The GSTM1 and GSTT1 null allele frequency distribution in the Gujarat population was significantly deviating from HWE. GSTT1 null frequency of Gujaratians was significantly higher and different to all reported low tobacco using Indian ethnics, while GSTM1 was not differing significantly. Conclusion: Tobacco usage significantly influences the rate of mutation and frequency of GSTT1 and M1 null types among the habituates. The rate of mutation in GSTT1 loci was an undeviating response to the dose of tobacco usage among the population. This mutational impact of tobacco on GSTT1 postulates the possible gene - environment interaction and selection of null genotype among the subjects to prone them under susceptible status for various cancers and even worst to cure the population with GSTT1 dependent drugs.

• Nutrition Research and Practice
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• 제12권2호
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• pp.118-128
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• 2018

BACKGROUND/OBJECTIVES: Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS: Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS: After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of ${\beta}-carotene$, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS: The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.

• 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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• 제16권15호
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• pp.6429-6438
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• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• 한국식품영양과학회지
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• 제36권6호
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• pp.708-719
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• 2007

본 연구에서는 104명의 성인남녀를 대상으로 그들의 GSTT1, GSTM1, GSTP1의 유전적 다형성 분포도를 조사한 결과, 전체 대상자들 중 각각 60명(57.4%), 42명(40.6%)가 GSTT1 과 GSTM1의 유전자를 가지고 있었으며, GSTT1과 GSTM1 유전자가 둘 다를 가진 대상자는 27명(25.7%), 둘 중에 하나만 가지고 있는 사람은 47명(45.5%) 그리고 둘 다 없는 사람은 30명으로 28.7%에 해당되었다. GSTP1 유전자의 경우 homozygous(a/a) wild type은 79명(75.5%)으로 대부분의 대상자가 여기에 해당되었으며, heterozygous(a/b) heterozygous type은 22명(21.6%), 그리고 homozygous(b/b) wild type으로 나타난 대상자는 3명(2.9%)이었다. GSTT1 null type은 산화적 스트레스를 더 많이 받고 있는 것으로 알려진흡연자의 비율이 present 군에 비해 낮음에도 불구하고 적혈구 GSH의 농도는 유의적으로 낮고 임파구 DNA 손상정도는 유의적으로 높은 것으로 나타났다. GSTM1 유전자의 경우 적혈구 GSH-Px의 활성만이 GSTM1 null type이 presenttype에 비해 유의적으로 높은 것으로 나타났으며, 나머지 다른 지표에서는 GSTM1 null type과 present type 간의 유의적인 차이가 없었다. GSTP1 유전자 다형성에 따른 항산화 영양상태의 유의적인 차이는 없었다. 흡연과 GST 유전자 다형성의 상호작용결과, 혈장 ${\alpha}$-carotene 농도, 적혈구 GSH-Px와 GST 활성은 GSTT1 null type의 경우 흡연자에 비해 비흡연자가 유의적으로 높게 나타났으며, GSTT1 present type에서는 흡연자와 비흡연자간의 유의적인 차이가 없는 것으로 나타났다. GSTM1 유전자의 경우 GSTM1의 null type에서 흡연자의 경우 비흡연자에 비해 혈장 ${\gamma}$-tocopherol과 ${\beta}$-carotene 수준이 유의적으로 낮았다. GSTT1과 GSTM1 유전자가 둘 다 없는 경우(both null)에는 흡연자의 혈장 lycopene과 적혈구 GST 활성이 비흡연자에 비해 유의적으로 낮았다. GSTP1 유전자의 경우 혈장 ${\alpha}$-carotene과 적혈구 GSH-Px 활성은 a/a type의 흡연자가 비흡연자에 비해 유의적으로 낮았고, 적혈구 catalase의 활성은 a/b type에서 흡연자가 비흡연자에 비해 유의적으로 낮았으며, ${\beta}$-carotene 농도는 두 type 모두에서 유의적으로 흡연자가 낮았다. 이상의 연구 결과 GST 유전적 다형성에따라 산화, 항산화 관련 효소 활성 및 항산화 영양소 수준의상태가 차이가 있음을 알 수 있었으며, 특히 흡연자의 경우 GST 유전자 type에 따라 항산화 영양상태가 더 큰 영향을 받음을 알 수 있었다. 이러한 연구 결과는 유전적 다형성에따라 항산화 영양소의 권장수준을 책정하는데 기초연구자료로 활용될 수 있을 것이다. 즉, GSTT1 또는 GSTM1 null type의 경우 비흡연자에 비해 흡연자가 항산화 영양소 수준이 더 낮게 나타났으므로 그들의 체내 항산화 영양 상태를 증가시킬 수 있는 여러 방안들, 즉 항산화 비타민의 보충투여 및 야채와 과일의 섭취 권장 등이 고려될 수 있을 것이다. 또한 GST 유전자 다형성에 따라 항산화 영양상태의 차이가 있으므로 항산화 관련 in vitro 실험, 동물 및 인체 실험의 결과 해석 시 나타나는 개인 간의 변이차이는 GST 유전자 다형성으로 일부분 설명될 수 있으리라 기대된다. 향후대상자의 범위를 좀 더 넓혀서 GST 유전자 다형성과 항산화 영양상태의 관계를 규명하고자 하며 더불어 산화물질 해독에 관여하는 다른 유전자(CYP 450, SULT 등)의 역할에 대해서도 계속적인 연구가 필요하다고 사료된다.