Glutathione S Transferase M1 Polymorphism in Extrahepatic Biliary Atresia

Background: Extrahepatic biliary atresia (EHBA) is a chronic progressive obstructive cholangiopathy of infancy of unknown aetiology. Pathology of bile duct damage involves unanimously neutrophil elastase, variable degrees of fibrosis, and variable CD14+ monocytes intensity staining in the presence of defective p53 and glutathione S transferases Pi class (GST Pi). GST is a super family responsible for detoxification of an array of substances that affect cellular replication and DNA fidelity, of them cytosolic GST Mu is a member. Aim of Work: Is to study GSTM1 gene polymorphism in EHBA. Material and Methods: Genotyping of GSTM1 from peripheral blood of 41 infants with EHBA, and from peripheral blood of their mothers was performed. Study commenced by July, 2001 and ended by July, 2004, in New Children Hospital, Cairo University. Results: All 41 enrolled infants had a null GSTM1 mutation concordant with homozygous deficiency, and all mothers expressed a pattern concordant with affection of only one allele. Conclusion: All infants suffering from EHBA had null GSTM1 genotype. Phenotypic loss of function of GSTM1 renders subjects with EHBA susceptible to a wide array of substances that affect cellular replication and DNA fidelity. Susceptibility to EHBA is genetic and transmitted in an autosomal recessive fashion from mothers with single gene allele. This work supports that EHBA is a developmental defect.