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 liver 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.
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 liver 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.
Authors: C P Day; R Bashir; O F James; M F Bassendine; D W Crabb; H R Thomasson; T K Li; H J Edenberg Journal: Hepatology Date: 1991-11 Impact factor: 17.425