Glutathione S Transferase Theta 1 Gene (GSTT1) Null Genotype Is Associated with an Increased Risk for Acquired Aplastic Anemia in Children

Dirksen, Uta; Moghadam, Kaveh Asadi; Mambetova, Chinara; Esser, Charlotte; Führer, Monika; Burdach, Stefan

doi:10.1203/01.pdr.0000111201.56182.fe

Cited by 27 publications

(34 citation statements)

References 49 publications

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“…There was no detectable enzyme activity in the individuals with GSTT1 null genotypes. It was has been reported that the absence of the GSTT1 enzymes might determine the individual risk for development of acquired aplastic anaemia in children (Dirksen et al 2004). In the present study there was a 1.91-fold increased risk of CBP in the individuals with the null GSTT1 genotype compared with the non-null GSTT1 genotype.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of chronic benzene poisoning in Chinese occupationally exposed populations

Chen

Yin

et al. 2007

Xenobiotica

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Benzene is a recognized haematotoxin and leukaemogen, but its mechanism of action and the role of genetic susceptibility are still unclear. Cytochrome P450 2E1 (CYP2E1) and myeloperoxidase (MPO) are involved in benzene activation; and NAD (P)H:quinine oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1) participate in benzene detoxification. The common, well-studied single-nucleotide polymorphisms (SNPs) were analysed in these genes drawn from the toxicant-metabolizing pathways. A total of 100 workers with chronic benzene poisoning (CBP) and 90 controls were enrolled in China. There was a 2.82-fold (95% CI = 1.42-5.58) increased risk of CBP in the subjects with the NQO1 609C > T mutation genotype (T/T) compared with those carrying heterozygous (C/T) and wild-type (C/C). The subjects with the GSTT1 null genotype had a 1.91-fold (95% CI = 1.05-3.45) increased risk of CBP compared with those with GSTT1 non-null genotype. There was no association of CYP2E1 and MPO genotype with CBP. A three genes' interaction showed that there was a 20.41-fold (95% CI = 3.79-111.11) increased risk of CBP in subjects with the NQO1 609C > T T/T genotype and with the GSTT1 null genotype and the GSTM1 null genotype compared with those carrying the NQO1 609C > T C/T and C/C genotype, GSTT1 non-null genotype, and GSTM1 non-null genotype. The study provides evidence of an association of a gene-gene interaction with the risk of CBP.

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Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of chronic benzene poisoning in Chinese occupationally exposed populations

Chen

Yin

et al. 2007

Xenobiotica

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“…Glutathione S-transferases are enzymes involved in the detoxification of several environmental mutagens, carcinogens, and anticancer drugs (phase II). Glutathione S-transferase polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors [10].…”

Section: Discussionmentioning

confidence: 99%

Study of genetic polymorphism of xenobiotic enzymes in acute leukemia

Eyada¹,

Ghonemy

Ghoroury

et al. 2007

Blood Coagulation &Amp; Fibrinolysis

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The work studied possible association between genetic polymorphisms of CYP2D6, GSTM1, GSTT1and NQO1 and altered susceptibility to leukaemia, correlating these genetic polymorphisms with clinical prognostic data, response to therapy and relapse. The study included 32 leukaemia patients, 19 with acute myeloid leukemia (AML) and 13 with acute lymphoid leukaemia (ALL), and 11 normal individuals (control group). Basic investigations for the diagnosis of AML and ALL were performed, including blood picture, bone marrow aspirate, cytochemistry and immunophenotyping for detection of subtypes. Detection of CYP2D6, NQO1, GSTM1 and GSTT1 genetic polymorphisms used a polymerase chain reaction-restriction fragment length polymorphism. A follow-up was made for association between the outcome of patients and different patterns of genetic polymorphisms. Results demonstrate a significant increase in the frequency of CYP2D6 wild-type and GSTM1 null genotypes in the acute leukaemia group compared with the control. Studying the relationship between polymorphisms of these genes and the outcome of our cases revealed the wild genotype of CYP2D6 significantly influenced the outcome of acute leukaemia particularly in AML cases, while GSTM1 null genotype was associated with bad prognosis among the ALL group. The study also revealed that patients with combined mutant CYP2D6/present GSTM1/present GSTT1 achieved the best prognosis, suggesting synergistic impact of these genetic polymorphisms on the outcome of acute leukaemia cases. This case-control study suggests a contribution of CYP2D6 and GSTM1 null variants in the development of acute leukaemia. In addition, GSTM1 and GSTT1 genotypes were apparently related to response, side effects and prognosis of patients with AML.

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“…Recent studies in Caucasian and Korean patients have shown increased incidence of AA in those with GSTM1 and GSTT1 null genotypes [14,15,16]. In the present study, the GSTM1 and GSTT1 null allele frequencies that we observed were different from those reported for the control Asian population [28] (GSTM1 null 32 vs. 47.6–60%, and GSTT1 null 21.5 vs. 35.3–51.9% in the present study versus reports from Japan, Korea and Singapore).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier reports on the incidence of AA and polymorphisms of CYP2D6 and CYP2E1 [13] have shown no significant difference in the frequencies of these polymorphisms in AA patients compared with normal controls. Polymorphisms of GSTM1 and GSTT1 have recently been shown to be associated with the occurrence of AA [14,15,16]. …”

Section: Introductionmentioning

confidence: 99%

Cytochrome P4501A1 and Glutathione S Transferase Gene Polymorphisms in Patients with Aplastic Anemia in India

et al. 2005

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The etiology of acquired aplastic anemia (AA) in most patients remains unclear. It is believed that patients with a reduced ability to detoxify environmental toxins are at increased risk of developing AA. Cytochrome P450 (CYP450) and glutathione S transferase (GST) are the major phase I and phase II xenobiotic-metabolizing enzymes. We analyzed the impact of the polymorphisms in CYP4501A1 and GSTM1 and GSTT1 genes on the susceptibility and disease severity in 200 patients with AA and compared the frequency with the normal population. There was a significantly increased frequency of the CYP1A1m4 allele in AA patients compared with normal controls (odds ratio = 3.01; 95% confidence interval 1.76–5.17; p = 0.00001). None of the other CYP1A1 genotypes or the GST genotypes were significantly different between AA patients and controls. Altered metabolism of benzo(a)pyrene due to the polymorphism in the CYP1A1 gene might be an etiologic factor in the increased incidence of AA in these patients. The CYP1A1m4 allele may play a role in determining the risk of AA in India.

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Glutathione S Transferase Theta 1 Gene (GSTT1) Null Genotype Is Associated with an Increased Risk for Acquired Aplastic Anemia in Children

Cited by 27 publications

References 49 publications

Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of chronic benzene poisoning in Chinese occupationally exposed populations

Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of chronic benzene poisoning in Chinese occupationally exposed populations

Study of genetic polymorphism of xenobiotic enzymes in acute leukemia

Cytochrome P4501A1 and Glutathione S Transferase Gene Polymorphisms in Patients with Aplastic Anemia in India

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