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Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1.

ABSTRACT: Glutathione S-transferases (GSTs) detoxify environmental chemicals and are involved in oxidative stress pathways. Deletion polymorphisms affect enzyme activities and have been associated with risk of disease.The objective was to clarify whether biomarkers of oxidation, antioxidation, inflammation, and nutritional factors differ by GST genotype in healthy adults.Subjects (n = 383) consisted of nonsmokers and nonusers of antiinflammatory drugs and antioxidant vitamin supplements. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped. F(2)-isoprostanes, malondialdehyde, C-reactive protein, serum vitamin C, carotenoids, tocopherols, and other nutritional factors were assessed.The concentration of serum vitamin C was higher in persons with the inactive GSTM1-0 genotype (P = 0.006). This relation was unchanged after adjustment for age, sex, BMI, or dietary vitamin C. F(2)-isoprostanes and malondialdehyde were lower in the GSTM1-0 and GSTT1-0 groups, respectively, but significance was lost after control for serum vitamin C. The dual deletion, GSTM1-0/GSTT1-0 (n = 37), was associated with higher serum iron and total and LDL-cholesterol concentrations (all P < 0.01) and lower malondialdehyde concentrations, which persisted after adjustment for age, sex, BMI, and serum vitamin C. Carotenoids and ?- and ?-tocopherols were not associated with either genotype.Oxidative stress and inflammation biomarkers differ by GST genotype, but serum vitamin C appears to be the most consistent factor. Examination of other relevant genes may be needed to understand the concentration and function of ascorbic acid in the GST enzyme system. This trial is registered at clinicaltrials.gov as NCT00079963.

SUBMITTER: Block G

PROVIDER: S-EPMC3155929 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1.

Block Gladys G Shaikh Nishat N Jensen Christopher D CD Volberg Vitaly V Holland Nina N

The American journal of clinical nutrition 20110803 3

<h4>Background</h4>Glutathione S-transferases (GSTs) detoxify environmental chemicals and are involved in oxidative stress pathways. Deletion polymorphisms affect enzyme activities and have been associated with risk of disease.<h4>Objective</h4>The objective was to clarify whether biomarkers of oxidation, antioxidation, inflammation, and nutritional factors differ by GST genotype in healthy adults.<h4>Design</h4>Subjects (n = 383) consisted of nonsmokers and nonusers of antiinflammatory drugs an ...[more]

PMID: 21813807

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Project description:BackgroundIt is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC.MethodsWe searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0).ResultsThe pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null.ConclusionsOur study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.

Project description:Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied. Atmospheric concentrations of benzene were measured and GSTM1 and GSTT1 genotypes were evaluated using the multiplex polymerase chain reaction (PCR) technique. Additionally, GSTP1 and CYP2E1 genotypes were determined by PCR- restriction fragment length polymorphism (PCR-RFLP). The frequency of null GSTT1 genotype in cases was significantly higher than that of referent group (32.3 vs. 18.5%, OR 2.1, 95% CI 1.23-3.56, p = 0.004). The mean value of platelets in subjects with null GSTT1 genotype was significantly lower than that of individuals with positive GSTT1 genotype (p = 0.015). Conversely, the mean value of leukocytes was significantly higher in subjects with null GSTM1 genotype as compared to those with positive GSTM1 genotype (p = 0.026). Logistic regression analysis showed that, subjects with null GSTT1 genotype had a significantly higher risk for hematological disorders, as compared to those with positive GSTT1 genotype (OR 2.1, 95% CI 1.23-3.56). Moreover, subjects with both null GSTT1 and GSTM1 genotypes had a significantly higher risk for hematological disorders as compared to subjects with positive GSTT1 and GSTM1 genotypes (OR 2.35, 95% CI 1.14-4.8). The results of this study showed that, individuals carrying null GSTT1 or both null STT1 and GSTM1 genotypes had a higher risk and were more susceptible to benzene-induced hematological disorders.

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Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1.

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Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1.

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