Page last updated: Tuesday, November 18, 2008
The Liver and Genetics Seminar Review by Dr Bernard Dixon OBE
There are unlikely to be genes that specifically and absolutely predispose a person to develop alcoholic liver disease and/or alcohol dependence. However, the next few years will probably see the discovery of genes that do contribute, in a quantifiable fashion, to the risk of both conditions. Such findings will mean that individuals can be screened for the relevant genes and counselled accordingly. They also raise questions about how society and the drinks industry should respond to a scenario in which a commercial product is particularly harmful to certain, identifiable individuals.

These conclusions emerged from a Portman Group seminar held on 23 March 2004 at the Westbury Hotel, London. The speakers were Professor Chris Day of the University of Newcastle upon Tyne, on the inheritance of alcoholic liver disease, and Professor Marc Schuckit of the University of California, San Diego, on the genetics of the risk of alcoholism. The event was chaired by Portman Group consultant Dr Bernard Dixon.

Professor Day observed that the risk of alcoholic liver disease (ALD) increases in proportion to alcohol intake (and that daily consumption is less hazardous than bingeing interspersed with alcohol-free days). Nevertheless, greater consumption does not account for the recent rise in ALD in Britain. The principal reason seems to be increasing obesity.

Still unclear is why most heavy drinkers do not develop ALD. Research on families, especially on twins, strongly indicates that some individuals are more susceptible than others for genetic reasons. Two likely types of candidate are the genes which make the enzymes that break down alcohol in the liver and those which produce cytokines, molecules involved in the body’s immune system.

Professor Schuckit estimated that multiple genetic factors combined together to explain 40-60% of the risk of alcohol abuse and dependence. Again, the role of heredity is apparent from the repeated observation that close relatives of alcoholics are three to four times more likely than other people to become alcoholics themselves. The increased relative risk is seen even among sons and daughters of alcoholics who have been adopted and raised away from the influence of an alcoholic parent. The same conclusion comes from comparisons between identical twins (who share all of the same genes) and non-identical twins (who do not share all of their genes).

Schuckit’s own research focuses not on “genes for alcoholism” per se but on those that determine characteristics which in turn affect the chances of an individual becoming alcoholic. One group of candidates are genes that influence a person’s response to alcohol and the level of intake at which they become intoxicated. Also under investigation are genes involved in the detoxification of alcohol by the liver - the same types of gene being studied for their influence on ALD.

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