Major genetic components underlying alcoholism in Korean population

Dai Jin Kim, Ihn Geun Choi, Byung Lae Park, Boung Chul Lee, Byung Joo Ham, Sujung Yoon, Joon Seol Bae, Hyun Sub Cheong, Hyoung Doo Shin

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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. 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 [odds ratio (OR) = 91.43, P = 1.4 × 10-32] and individuals bearing one susceptible and one protective allele at either loci have 11 times greater risk (OR = 11.40, P = 3.5 × 10-15) compared with subjects who have both protective alleles. The attributable fraction 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.

Original languageEnglish
Pages (from-to)854-858
Number of pages5
JournalHuman Molecular Genetics
Volume17
Issue number6
DOIs
StatePublished - 15 Mar 2008

Bibliographical note

Funding Information:
This work was supported by a grant from the National Research Lab Program as part of the National Research and Development Program of the Ministry of Commerce, Industry and Energy of Korea (M1-0302-00-0073). This study was also partly supported by a grant from Biomedical Brain Research Center (A040042) and a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare (03-PJ10-PG13-GD01-0002) funded by the Ministry of Health & Welfare, Republic of Korea.

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