Alcohol and Alcoholism Advance Access originally published online on February 21, 2006
Alcohol and Alcoholism 2006 41(3):209-224; doi:10.1093/alcalc/agl011
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REVIEW
THE ROLE OF GENETIC POLYMORPHISMS IN ALCOHOLIC LIVER DISEASE
1 Institute of Clinical Pharmacology, University of Berne, Switzerland and 2 Department of Medicine, Columbia University, NY, USA
* Author to whom correspondence should be addressed at: Institute of Clinical Pharmacology, University of Berne, Murtenstraße 35, CH-3010 Berne, Switzerland. Tel.: +41 31 632 8715; Fax: +41 31 632 4997; E-mail: felix.stickel{at}ikp.unibe.ch
Received 13 December 2005; accepted 3 January 2006
Chronic alcohol consumption is a major cause of liver cirrhosis which, however, develops in only a minority of heavy drinkers. Evidence from twin studies indicates that genetic factors account for at least 50% of individual susceptibility. The contribution of genetic factors to the development of diseases may be investigated either by means of animal experiments, through linkage studies in families of affected patients, or population based case–control studies. With regard to the latter, single nucleotide polymorphisms of genes involved in the degradation of alcohol, antioxidant defense, necroinflammation, and formation and degradation of extracellular matrix are attractive candidates for studying genotype–phenotype associations. However, many associations in early studies were found to be spurious and could not be confirmed in stringently designed investigations. Therefore, future genotype–phenotype studies in alcoholic liver disease should meet certain requirements in order to avoid pure chance observations due to a lack of power, false functional interpretation, and insufficient statistical evaluation.
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