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Human Molecular Genetics Advance Access published online on December 4, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm357
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Major Genetic Components Underlying Alcoholism in Korean Population

Dai-Jin Kim1, Ihn-Geun Choi2, Byung Lae Park3, Boung-Chul Lee2, Byung-Joo Ham2, Sujung Yoon1, Joon Seol Bae3, Hyun Sub Cheong3 and Hyoung Doo Shin3,*

1 Department of Psychiatry, Holy Family Hospital, College of Medicine, Catholic University of Korea, Sosa-dong, Wonmi-Gu, Pucheon, Kyounggi-do, Korea, 420-717 2 Department of Neuropsychiatry, Hallym University, Han-Gang Sacred Heart Hospital, 94-200 Youngdungpo-Dong, Youngdungpo-Gu, Seoul, Korea, 150-719 3 Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul, Korea, 153-801

* Correspondence and request for reprints should be addressed to: Dr. Hyoung Doo Shin, Department of Genetic Epidemiology, SNP Genetics, Inc., Rm 1407, 14th floor, Complex B, WooLim Lion's Valley, 371-28, Gasan-Dong, Geumcheon-Gu, Seoul, Korea, 153-801. Tel: 82-2-2026-4288; Fax: 82-2-2026-4299; E-mail: hdshin{at}snp-genetics.com

Received October 1, 2007; Revised November 30, 2007; Accepted November 30, 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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