Din. Sherman et al., ASSOCIATION OF RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM IN ALCOHOL DEHYDROGENASE-2 GENE WITH ALCOHOL-INDUCED LIVER-DAMAGE, BMJ. British medical journal, 307(6916), 1993, pp. 1388-1390
Objective-To investigate the role of genetically determined difference
s in the enzymes of alcohol metabolism in susceptibility to liver dama
ge from misusing alcohol. Design-Use of pADH36 probe to study PVU II r
estriction length fragment polymorphism in alcohol dehydrogenase 2 gen
e in white alcohol misusers and controls. Setting-Teaching hospital re
ferral centres for fiver disease and alcohol misuse. Subjects-45 white
alcohol misusers (38 with alcoholic liver disease) and 23 healthy con
trols. 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 ident
ified. In control subjects the allele frequencies were 85% for A and 1
5% for B compared with 37% and 63% respectively in alcohol misusers (p
< 0.001). B allele was significantly associated with severe liver dam
age (p < 0.05) as well as alcohol dependency and family history of alc
ohol misuse compared with controls. Conclusion-Inherited variation in
enzymes of ethanol metabolism may contribute to the pathogenesis of al
cohol induced liver damage. This supports the presence of a genetic co
mponent in alcohol misuse.