Association of Restriction Fragment Length Polymorphism in Alcohol Dehydrogenase 2 Gene with Alcohol Induced Liver Damage.

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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.

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