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Major genetic components underlying alcoholism in Korean population
Dai-Jin Kim1, Ihn-Geun Choi, Byung Lae Park
1Department of Psychiatry, Holy Family Hospital, College of Medicine, Catholic University of Korea, Sosa-dong, Wonmi-Gu, Pucheon, Kyounggi-do 420-717, Republic of Korea.
Human Molecular Genetics
|December 7, 2007
Summary
Genetic variations in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) significantly impact alcoholism risk. Specific ADH1B and ALDH2 gene variants dramatically increase alcoholism risk, especially when combined.
Area of Science:
- Pharmacogenetics
- Human Genetics
- Alcoholism Research
Background:
- Alcohol metabolism is influenced by genetic polymorphisms in key enzymes like alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
- ADH converts alcohol to acetaldehyde, while ALDH converts acetaldehyde to acetate, with genetic variations affecting these rates.
- Known polymorphisms in ADH1B and ALDH2 genes significantly alter alcohol and acetaldehyde metabolism, respectively.
Purpose of the Study:
- To investigate the combined genetic effects of ADH1B and ALDH2 polymorphisms on alcoholism risk.
- To clarify the interaction between rapid alcohol-metabolizing ADH1B alleles and slow acetaldehyde-metabolizing ALDH2 alleles.
Main Methods:
- A population-based study involving 1,032 Korean individuals.
- Analysis of combined genotypes for ADH1B (His47Arg) and ALDH2 (Glu487Lys) polymorphisms.
- Calculation of odds ratios (OR) and attributable fractions for alcoholism risk.
Main Results:
- Individuals with susceptible alleles at both ADH1B and ALDH2 loci showed a 91-fold increased risk of alcoholism (OR = 91.43).
- Carriers of one susceptible and one protective allele at either locus had an 11-fold increased risk (OR = 11.40) compared to those with two protective alleles.
- Genetic factors, specifically ADH1B*47Arg and/or ALDH2*487Glu, were found to account for 86.5% of alcoholism cases in the Korean population.
Conclusions:
- Combined genetic polymorphisms in ADH1B and ALDH2 have a dramatic synergistic effect on alcoholism risk.
- These genetic variations are significant determinants of alcoholism, particularly in the Korean population.
- Targeting individuals with these high-risk genotypes could inform prevention and intervention strategies for alcoholism.
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