Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans

Dušinská, Maria; Ficek, Andrej; Horská, Alexandra; Rašlová, K; Petrovská, Helena; Vallová, B; Drličková, Martina; Wood, Sharon; Stupakova, Alexandra; Gašparovič, Juraj; Bobek, P; Nagyová, A; Kovačíková, Zuzana; Blažı́ček, P; Liegebel, Ute; Collins, Andrew

doi:10.1016/s0027-5107(01)00209-3

Cited by 128 publications

(74 citation statements)

References 16 publications

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“…However, protective GSTT1 genotype was associated with higher vitamin C level and glucose-6-phosphate dehydrogenase activity, than those observed in GSTT1 null genotype. GST activity measured in lymphocytes was significantly higher in carriers of GSTP1 codon 105 than in wild-type genotypes [5].…”

Section: Discussionmentioning

confidence: 81%

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

2007

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Section: Discussionmentioning

confidence: 81%

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

2007

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“…40 Homozygous GSTP1 AA genotype is associated with significantly higher levels of GST activity measured in lymphocytes. 41 Moreover, recent investigations, have uncovered that members of GSTs and related proteins could express multifunctional activities including modulation of T lymphocyte function. 42 Further experimental and clinical studies should confirm and explore these results.…”

Section: Discussionmentioning

confidence: 99%

Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia

et al. 2008

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Individual differences in drug efficacy or toxicity can be influenced by genetic factors. We investigated whether polymorphisms of pharmacogenes that interfere with metabolism of drugs used in conditioning regimen and graft-versus-host disease (GvHD) prophylaxis could be associated with outcomes after HLA-identical hematopoietic stem cell transplantation (HSCT). Pharmacogenes and their polymorphisms were studied in 107 donors and patients with leukemia receiving HSCT. Candidate genes were: P450 cytochrome family (CYP2B6), glutathione-S-transferase family (GST), multidrug-resistance gene, methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR). The end points studied were oral mucositis (OM), hemorrhagic cystitis (HC), toxicity and venoocclusive disease of the liver (VOD), GvHD, transplantationrelated mortality (TRM) and survival. Multivariate analyses, using death as a competing event, were performed adjusting for clinical factors. Among other clinical and genetic factors, polymorphisms of CYP2B6 genes that interfere with cyclophosphamide metabolism were associated with OM (recipient CYP2B6*4; P ¼ 0.0067), HC (recipient CYP2B6*2; P ¼ 0.03) and VOD (donor CYP2B6*6; P ¼ 0.03). Recipient MTHFR polymorphisms (C677T) were associated with acute GvHD (P ¼ 0.03), and recipient VDR TaqI with TRM and overall survival (P ¼ 0.006 and P ¼ 0.04, respectively).Genetic factors that interfere with drug metabolisms are associated with treatment-related toxicities, GvHD and survival after HLA-identical HSCT in patients with leukemia and should be investigated prospectively.

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“…It belongs to the family of phase II antioxidant enzymes involved in the cellular detoxification of various physiological substances [7]. It constitutes the major defensive antioxidant system against oxidative stress by reducing ROS to less reactive metabolites [8]. Polymorphisms in the GST gene may impair the ability of protection against oxidative stress and lead to the development of a wide range of diseases [9].…”

Section: Introductionmentioning

confidence: 99%

Association of the Glutathione S-transferases M1 and T1 polymorphism with male infertility: a meta-analysis

Song

Zhao

Cai

et al. 2012

J Assist Reprod Genet

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Background Genes of different pathways regulate spermatogenesis, and the complexity of the spermatogenic process indicates that polymorphisms or mutations in these genes could cause male infertility. Published data on the association between the GSTM1 and GSTT1 polymorphism and male infertility risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods A total of 11 studies regarding GSTM1 and 9 studies regarding GSTT1 between 1999 and 2012 were identified through researching MEDLINE, EMBASE and the Chinese Biomedical Database. It was performed to obtain summary estimated odd ratios and 95 % confidence intervals of GSTM1 and GSTT1 for male infertility, with attention to study quality and publication bias. Results Overall, a significant association was seen between GSTM1 (OR01.20, 95 % CI 01.02-1.40, P heterogeneity 0 0.000, P00.027) genotypes and male infertility. Significant associations were also observed in subgroups of Caucasian populations (OR01.65, 95 %CI01.16-2.34, P heterogeneity 0 0.006, P00.005), but were not observed in Asian populations (OR01.09, 95 % CI00.72-1.65, P heterogeneity 00.054, P00.697) when stratified by ethnicity. While there was no significant association was seen between GSTT1 (OR0 1.00, 95 % CI00.74-1.35, P heterogeneity 00.000, P00.980) null genotypes and male infertility. Simultaneously, significant associations were not observed in subgroups of Caucasian populations (OR 00.94, 95 %CI 00.44-2.00, P heterogeneity 00.000, P 00.867) and Asian populations (OR00.93, 95 % CI00.46-1.87, P heterogeneity 00.002, P0 0.838) when stratified by ethnicity. Conclusion Our results suggest the GSTM1 null genotype contributes to male infertility susceptibility, while GSTT1 gene polymorphisms are not associated with male infertility in our study.

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Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans

Cited by 128 publications

References 16 publications

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia

Association of the Glutathione S-transferases M1 and T1 polymorphism with male infertility: a meta-analysis

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