title: Genetic polymorphisms of glutathione-S-transferase and microsomal epoxide hydrolase in egyptian acquired aplastic anemia patients.
abstract: Exposure to various environmental toxins with a reduced ability to metabolize them may lead to acquired aplastic anemia (AA). Genetic polymorphism of the detoxifying enzymes, the glutathione-S-transferase (GST) and microsomal epoxide hydrolase (mEh), with alteration in their activities could explain the genetic interindividual risks for AA. We aimed to characterize the genetic polymorphisms of the GST and mEh and to test their impact on the susceptibility, disease severity, and prognosis in Egyptian patients with AA. The GST and mEh genotypes were determined by multiplex-polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analysis, respectively, in 21 patients with AA and 20 healthy control subjects. The mEh functional phenotypes were assessed. The frequency of GST θ1-null genotype was found significantly higher in AA patients compared with the controls (odds ratio=2.8, 95% confidence interval = 1.1-7.8; P = 0.001). The frequency of heterozygous 139A--G of the mEh gene was significantly higher in AA patients compared with the controls (odds ratio=3.07, 95% confidence interval = 1.23-7.7; P = 0.018). Moreover, the patients with normal functional phenotype of the mEh had significantly favorable prognosis than those with abnormal enzyme activity (P = 0.027). Thus, the GST θ1-null genotype and the 139A--G mEh gene polymorphism may enhance the susceptibility to AA and provide an evidence of gene-environmental interaction.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt. ilhamyoussry@yahoo.com
authors.forename: Ilham
authors.initials: I
authors.lastname: Youssry
authors.forename: Rania
authors.initials: R
authors.lastname: Hammoud
authors.forename: Ola
authors.initials: O
authors.lastname: Ibrahim
authors.forename: Mai
authors.initials: M
authors.lastname: Youssef
authors.forename: Amal
authors.initials: A
authors.lastname: Beshlawy
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000201:enzymology* / Q000235:genetics*; D002648:Child; D004534:Egypt; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005982:Glutathione Transferase; D004851:Epoxide Hydrolases