Major genetic components underlying alcoholism in Korean population.
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.
Kim
Dai-Jin
DJ
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.
Choi
Ihn-Geun
IG
Park
Byung Lae
BL
Lee
Boung-Chul
BC
Ham
Byung-Joo
BJ
Yoon
Sujung
S
Bae
Joon Seol
JS
Cheong
Hyun Sub
HS
Shin
Hyoung Doo
HD
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000483:Alleles; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase