Research Article

Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver damage.

BMJ 1993; 307 doi: (Published 27 November 1993) Cite this as: BMJ 1993;307:1388
  1. D I Sherman,
  2. R J Ward,
  3. M Warren-Perry,
  4. R Williams,
  5. T J Peters
  1. Department 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.