Human Molecular Genetics Advance Access originally published online on December 4, 2007
Human Molecular Genetics 2008 17(6):854-858; doi:10.1093/hmg/ddm357
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Major genetic components underlying alcoholism in Korean population
1 Department of Psychiatry, Holy Family Hospital, College of Medicine, Catholic University of Korea, Sosa-dong, Wonmi-Gu, Pucheon, Kyounggi-do 420-717, Republic of Korea 2 Department of Neuropsychiatry, Hallym University, Han-Gang Sacred Heart Hospital, 94-200 Youngdungpo-Dong, Youngdungpo-Gu, Seoul 150-719, Republic of Korea 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 153-801, Republic of Korea
* To whom correspondence should be addressed. Tel: +82 220264288; Fax: +82 220264299; Email: hdshin{at}snp-genetics.com
Received October 1, 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. 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 x 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 x 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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.