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 language | English |
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Pages (from-to) | 854-858 |
Number of pages | 5 |
Journal | Human Molecular Genetics |
Volume | 17 |
Issue number | 6 |
DOIs | |
State | Published - 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.