Genetic polymorphisms of glutathione-S-transferase and microsomal epoxide hydrolase in acquired aplastic anemia

Glutathione-S-transferase [GST] and microsomal epoxide hydrolase [mEh] are detoxifing enzymes that modulate the effects of exposure to various environmental cytotoxic and genotoxic agents, including those associated with increased risk of acquired aplastic anemia [AAA]. The GST mu1 [GSTM1], GST the ta1 [GSTT1] and mEh genes have polymorphisms with functional alteration that could explain the interindividual risks for AAA. To determine the frequency of GST and mEh polymorphisms as a risk factor for the susceptibility, clinical severity and response to treatment in a group of Egyptian paediatric patients with AAA. GST and mEh genotypes were determined by multiplex-PCR and PCR-RFLP analysis respectively in 21 patients with AAA and 20 healthy matched control subjects. The mEh enzyme activities genotypes were assessed. The incidence of the GSTT1 null genotype was significantly higher in AAA patients compared with the controls [85.7% vs. 50%] [OR 2.8, 95% CI 1.1-7.8, p=0.01]. The incidence of the heterozygous arginine [Arg] 139 polymorphism in exon 4 of the mEh gene was significantly higher in AAA patients compared with the controls [61.9% vs. 20%], [OR 3.07; 95% CI, 1.23-7.7, p=0.005]. The incidence of the fast mEh activity genotype was significantly higher in AAA patients compared with the controls [33.3% vs. 15%] [OR 2.9; 95% CI, 1.09-8.9, p=0.03]. Most patients with normal functional phenotype responded significantly favorably to treatment than patients with abnormal enzyme activity [p=0.027]. Genetic polymorphisms in biotransformation enzymes: GSTT1-null genotype, mEh His/Arg polymorphism and fast putative functional activity could be considered as risk factors to develop AAA. Moreover, abnormal functional activity of mEh enzyme was associated with worse prognosis of the disease

Lipid peroxidation and its relation to serum bilirubin and uric acid as antioxidants in neonatal hyperbilirubinemia

The fact that almost alt neonates exhibit a physiological jaundice, prompt the question whether bitirubin, usually considered a potentially toxic end product of heme metabolism, might also have a beneficial role in the first few days of life. There was increasing flow evidences that bilirubin has antioxdant property and can effectively inhibit lipid peroxidation. We aimed to study the relationship between bilirubin and malondialdehyde [MDA] and uric acid [UA] in full term babies with hyperbilirubinemia in the first few days of life. A total of 73 full term newborn infants were included in this study, 58 newborns with significant hyperbilirubinemia [total bilirubin >/= 12.9 mg%] and 15 sex and age matched controls. The hyperbilirubinemic neonates were divided into 2 groups according to presence or absence of hemolysis. Total serum bilirubin, serum MDA [as a marker of lipid peroxidation] and UA [as an antioxidant] concentrations were determined in all studied neonates. There were significant differences in mean total serum bilirubin, MDA and uric acid between hyperbilirubinemic neonates and control group [p < 0.01], also between neonates with and without hemolysis. [p < 0.01]. A positive correlation was found between MDA and bilirubin concentrations in the hyperbilirubinemic neonates When the study group was categorized according to the presence of hemolysis, a significant correlation was found between MDA and bilirubin concentrations in neonates with hyperbilirubinaemia due to hemolysis and there was no significant correlation in those without hemolysis. We conclude that bilirubin has an important physiologic function as an antioxidant and may play a role in the prevention of oxidative damage