THE GENETICS OF ALCOHOLISM: IS THERE AN INHERITED SUSCEPTIBILITY TO ALCOHOL-RELATED PROBLEMS? |
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Authors: | SAUNDERS, J. B. WILLIAMS, ROGER |
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Affiliation: | The Liver Unit, King's College Hospital and Medical School London, SE5, U.K. |
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Abstract: | Alcoholism and alcohol-related disorders have a pronounced familialtendency. There has been considerable debate over many yearsas to whether this represents transmission of genetic traitsor the influence of family environment on drinking behaviour.Studies of adopted children and of monozygotic compared withdizygotic twins show a modest but definite genetic influenceon drinking habits and, at least in men, on the occurrence ofpsychosocial problems related to alcohol abuse. There is evidencefor two types of alcoholism, one that is highly heritable andanother that shows a lesser degree of inheritance and requiresenvironmental stressors for it to be manifest. The mechanismsby which such genetic influences are expressed are unknown althoughthe metabolism of alcohol and many of its physiological effectsare partly genetically determined. No biological markers havebeen associated convincingly with a predisposition to alcoholismbut absence of an isoenzyme of aldehyde dehydrogenase, whichoccurs in 50% of Oriental populations, has been related to thealcohol-flush reaction which may have an aversive effect onalcohol consumption. This may explain the low incidence of alcoholproblems in Oriental countries. Genetic factors have long been thought to be responsible forthe variation in susceptibility to the physical sequelae ofchronic alcohol consumption such as cirrhosis and cardiomyopathy.Women develop many complications of alcoholism, especially liverdisease, after a shorter period of drinking and at a lower dailyalcohol intake than men, and this is partly related to differencesinbody size and composition and in hormonal status. Several hiitocompatibility(HLA) antigens have been linked to susceptibility to cirrhosis.The association for most is relatively weak but HLA-B8 and DR3are associated with accelerated development of cirrhosis, possiblyby stimulating cytotoxic immune reactions to alcohol-damagedliver cells. Little is known about what genetic factors mightpredispose to other alcohol-related diseases. Further work into the mechanisms by which genetic factors influencethe development of alcoholism and susceptibility to its complicationsmay help identify agents that interfere with these processes.Total abstinence from alcohol may be advisable for family membersof subjects with the highly heritable form of alcoholism. Untilmore is known about individual safe limits for drinking everyoneshould be advised to keep below 80g alcohol/day (for men) or40g/day (for women). |
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