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        Polymorphism Underlies Liver Disease In Paediatric Cystic Fibrosis

        A DGReview of :"Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism."
        Hepatology

        10/11/2002
        By David Loshak


        Children with cystic fibrosis and liver disease have far higher frequency of the GSTP1-Ile(105)-encoding allele than children with cystic fibrosis who do not have liver disease.

        In younger children (age 6 years) this genotype was found to be associated with a risk of liver disease up to eight times higher than closely related genotypes, French researchers report.

        The researchers note that liver disease has inconstant prevalence in patients with cystic fibrosis, and until now, it has not yet been clearly related to any specific risk factor.

        While the expression of cystic fibrosis transmembrane conductance regulator was restricted to the biliary epithelium in the liver, recent findings have indicated that this regulator modulated reduced glutathione transport. Also, the researchers observed, cystic fibrosis transmembrane conductance regulator dysfunction created an imbalance in antioxidant defence. And among liver detoxifying enzymes, the glutathione S-transferases (GSTs) plays a key protective role against oxidative stress.

        Because oxidative injury contributes to the development of liver disease, the researchers looked into whether two members of the glutathione S-transferase super-family expressed in the biliary epithelium -- GSTM1 and GSTP1 -- could influence hepatic status. They assessed the potential impact of GSTM1 and GSTP1 gene polymorphisms in 106 children with cystic fibrosis, mean age 11.5 years.

        Using polymerase chain reaction/restriction fragment length polymorphism analysis, the researchers found that the frequency of GSTP1-Ile(105) genotype was significantly higher in the children with liver disease. In the youngest patients, those aged six years, the genotype was associated with an eight-fold increase in the risk of liver disease compared with other GSTP1 genotypes.

        No association between the GSTM1 genotype and liver status was documented.

        They suggest that spotting the allele might prompt early treatment of cystic fibrosis patients at increased risk of liver disease. The polymorphism contributed to hepatic dysfunction in cystic fibrosis, they write, so identifying it might have prognostic value.
        Hepatology 2002;36(4/1):913-917. "Liver disease in pediatric patients with cystic fibrosis is associated with glutathione S-transferase P1 polymorphism."

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