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Monday, December 10, 2007

Major Genetic Components Underlying Alcoholism in Korean Population
Human Molecular Genetics Advance Access published online on December 4, 2007



Alcohol metabolism is one of the biological determinants that could significantly be influenced by genetic polymorphisms in alcohol-metabolism genes.

Alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde, and aldehyde dehydrogenase (ALDH) converts acetaldehyde to acetate. The well-known genetic polymorphisms in ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of metabolizing alcohol and acetaldehyde, respectively (1-6).

The protective allele of ADH1B (ADH1B*47His) encodes for a rapid ethanol-metabolizing enzyme, and the susceptible allele of the ALDH2 (ALDH2*487Lys) is strongly associated with decreased rate of metabolizing acetaldehyde.

However, the combined genetic effects of both functional polymorphisms have not been clarified.

The combined analysis of two polymorphisms among a Korean population (n=1,032) revealed dramatic genetic effects on the risk of alcoholism. Individuals bearing susceptible alleles at both loci have 91 times greater risk for alcoholism (OR=91.43, P=1.4x 10–32) and individuals bearing one susceptible and one protective allele at either loci have 11 times greater risk (OR=11.40, P=3.5x10–15) compared with subjects who have both protective alleles.

The attributable fraction (AF) of those genetic factors, calculated based on population controls, indicates that alcoholism in 86.5% of alcoholic patients can be attributed to the detrimental effect of ADH1B*47Arg and/or ALDH2*487Glu in Korean population.

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