ASSOCIATION OF RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM IN ALCOHOL DEHYDROGENASE-2 GENE WITH ALCOHOL-INDUCED LIVER-DAMAGE

Objective-To investigate the role of genetically determined differences in the enzymes of alcohol metabolism in susceptibility to liver damage from misusing alcohol. Design-Use of pADH36 probe to study PVU II restriction length fragment polymorphism in alcohol dehydrogenase 2 gene in white alcohol misusers and controls. Setting-Teaching hospital referral centres for fiver disease and alcohol misuse. Subjects-45 white alcohol misusers (38 with alcoholic liver disease) and 23 healthy controls. Main outcome measures-Alcohol misuse, the presence and severity of alcoholic liver disease, alcohol dependency, and family history of alcohol misuse. Results-A two allele polymorphism (A and B) was identified. In control subjects the allele frequencies were 85% for A and 15% for B compared with 37% and 63% respectively in alcohol misusers (p < 0.001). B allele was significantly associated with severe liver damage (p < 0.05) as well as alcohol dependency and family history of alcohol misuse compared with controls. Conclusion-Inherited variation in enzymes of ethanol metabolism may contribute to the pathogenesis of alcohol induced liver damage. This supports the presence of a genetic component in alcohol misuse.