GSTM1 NULL POLYMORPHISM AT THE GLUTATHIONE S-TRANSFERASE M1 LOCUS IN CHILDHOOD LIVER DISEASE. • 253

Glutathlone S-transferases (alpha, mu, theta, and pi) are a family of detoxifying enzymes which catalyze the conjugation of glutathione to electrophilic compounds. About 50% of the human population has the GSTM1 0/0 genotype resulting in the lack of the mu transferase enzyme. This population has approximately 50% less total hepatic glutathione S-transferase activity. It has been suggested that this genotype is associated with an increased risk of toxin-induced disease. For example, adults with alcohol-induced liver disease have an increased frequency of the GSTM1 0/0 genotype, while adults with primary biliary cirrhosis do not. No published data exists on the frequency of the GSTM1 0/0 genotype in childhood liver diseases.Purpose: To establish the frequency of the GSTM1 0/0 genotype in children who receive liver transplantation for biliary atresia/cirrhosis, hepatitis, or α₁ antitrypsin deficiency. Methods: DNA was purified from native liver specimens from children undergoing liver transplantation, and from donor splenocytes. Differential PCR amplification was used to evaluate the GSTM1 genotype in 137 donor spleen specimens and 178 recipient liver specimens. Results: The GSTM1 0/0 frequency observed was 48% (66/137) in controls, 54% (54/100) in children with biliary atresia/biliary cirrhosis, 65% (17/26) in children with α₁ antitrypsin deficiency, and 44% (22/50) in children with hepatitis. Children with α₁ antitrypsin deficiency showed a trend towards an increased frequency of GSTM1 0/0 compared to controls (p=0.10, Chi-Square).Conclusions: The GSTM1 0/0 genotype does not appear to be an important risk factor for the development of liver failure in children with biliary atresia/cirrhosis or hepatitis. Increased patient numbers will be necessary to determine whether an increased GSTM1 0/0 genotype frequency occurs in children with liver failure secondary to α₁ antitrypsin deficiency.