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Alcohol and Alcoholism Advance Access published online on February 21, 2006
Alcohol and Alcoholism, doi:10.1093/alcalc/agl011
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved
Received December 13, 2005
Accepted January 3, 2006

Review

THE ROLE OF GENETIC POLYMORPHISMS IN ALCOHOLIC LIVER DISEASE

FELIX STICKEL 1 * and CHRISTOPH H. ÖSTERREICHER 2

1 Institute of Clinical Pharmacology, University of Berne, Switzerland
2 Department of Medicine, Columbia University, NY, USA

* To whom correspondence should be addressed.
FELIX STICKEL, E-mail: felix.stickel{at}ikp.unibe.ch


  Abstract

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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