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Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver
D I Sherman1, R J Ward, M Warren-Perry
1Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London.
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.