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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1989 January; 83(1): 314–316.
PMCID: PMC303676

Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant.


Many Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity responsible for the oxidation of acetaldehyde produced during ethanol metabolism. These individuals suffer the alcohol-flush reaction when they drink alcoholic beverages. The alcohol-flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. The subunit of this homotetrameric enzyme was sequenced and the abnormality in the inactive enzyme shown to be a substitution of lysine for glutamate at position 487. We have used the polymerase chain reaction to determine the genotypes of 24 livers from Japanese individuals. Correlating genotype with phenotype leads to the conclusion that the allele (ALDH2(2)) encoding the abnormal subunit is dominant.

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Selected References

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  • Goedde HW, Agarwal DP. Polymorphism of aldehyde dehydrogenase and alcohol sensitivity. Enzyme. 1987;37(1-2):29–44. [PubMed]
  • Hsu LC, Yoshida A, Mohandas T. Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2. Am J Hum Genet. 1986 May;38(5):641–648. [PubMed]
  • Goedde HW, Harada S, Agarwal DP. Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet. 1979 Oct 2;51(3):331–334. [PubMed]
  • Harada S, Misawa S, Agarwal DP, Goedde HW. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. Am J Hum Genet. 1980 Jan;32(1):8–15. [PubMed]
  • Goedde HW, Agarwal DP, Harada S. Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots. Enzyme. 1980;25(4):281–286. [PubMed]
  • Mizoi Y, Ijiri I, Tatsuno Y, Kijima T, Fujiwara S, Adachi J, Hishida S. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Pharmacol Biochem Behav. 1979 Feb;10(2):303–311. [PubMed]
  • Harada S, Agarwal DP, Goedde HW. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet. 1981 Oct 31;2(8253):982–982. [PubMed]
  • Bosron WF, Rex DK, Harden CA, Li TK, Akerson RD. Alcohol and aldehyde dehydrogenase isoenzymes in Sioux North American Indians. Alcohol Clin Exp Res. 1988 Jun;12(3):454–455. [PubMed]
  • Goedde HW, Agarwal DP, Harada S, Rothhammer F, Whittaker JO, Lisker R. Aldehyde dehydrogenase polymorphism in North American, South American, and Mexican Indian populations. Am J Hum Genet. 1986 Mar;38(3):395–399. [PubMed]
  • Teng YS. Human liver aldehyde dehydrogenase in Chinese and Asiatic Indians: gene deletion and its possible implications in alcohol metabolism. Biochem Genet. 1981 Feb;19(1-2):107–114. [PubMed]
  • Hempel J, Kaiser R, Jörnvall H. Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations. Eur J Biochem. 1985 Nov 15;153(1):13–28. [PubMed]
  • Ikawa M, Impraim CC, Wang G, Yoshida A. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983 May 25;258(10):6282–6287. [PubMed]
  • Yoshida A, Huang IY, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. Proc Natl Acad Sci U S A. 1984 Jan;81(1):258–261. [PubMed]
  • Impraim C, Wang G, Yoshida A. Structural mutation in a major human aldehyde dehydrogenase gene results in loss of enzyme activity. Am J Hum Genet. 1982 Nov;34(6):837–841. [PubMed]
  • Yoshida A, Wang G, Davé V. Determination of genotypes of human aldehyde dehydrogenase ALDH2 locus. Am J Hum Genet. 1983 Nov;35(6):1107–1116. [PubMed]
  • Schwitters SY, Johnson RC, Johnson SB, Ahern FM. Familial resemblances in flushing following alcohol use. Behav Genet. 1982 May;12(3):349–352. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Harada S, Agarwal DP, Goedde HW. Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing. Hum Genet. 1978 Jan 19;40(2):215–220. [PubMed]
  • Johnson CT, Bosron WF, Harden CA, Li TK. Purification of human liver aldehyde dehydrogenase by high-performance liquid chromatography and identification of isoenzymes by immunoblotting. Alcohol Clin Exp Res. 1987 Feb;11(1):60–65. [PubMed]
  • Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ. Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics. 1988 Apr;2(3):209–214. [PubMed]
  • Hsu LC, Bendel RE, Yoshida A. Genomic structure of the human mitochondrial aldehyde dehydrogenase gene. Genomics. 1988 Jan;2(1):57–65. [PubMed]
  • Hsu LC, Bendel RE, Yoshida A. Direct detection of usual and atypical alleles on the human aldehyde dehydrogenase-2 (ALDH2) locus. Am J Hum Genet. 1987 Dec;41(6):996–1001. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Ferencz-Biro K, Pietruszko R. Human aldehyde dehydrogenase: catalytic activity in oriental liver. Biochem Biophys Res Commun. 1984 Jan 13;118(1):97–102. [PubMed]
  • Harada S, Agarwal DP, Goedde HW, Tagaki S, Ishikawa B. Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan. Lancet. 1982 Oct 9;2(8302):827–827. [PubMed]
  • Harada S, Agarwal DP, Goedde HW, Ishikawa B. Aldehyde dehydrogenase isozyme variation and alcoholism in Japan. Pharmacol Biochem Behav. 1983;18 (Suppl 1):151–153. [PubMed]
  • Harada S, Agarwal DP, Goedde HW. Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics. Alcohol. 1985 May-Jun;2(3):391–392. [PubMed]
  • Yoshihara H, Sato N, Kamada T, Abe H. Low Km ALDH isozyme and alcoholic liver injury. Pharmacol Biochem Behav. 1983;18 (Suppl 1):425–428. [PubMed]
  • Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science. 1987 Apr 24;236(4800):410–416. [PubMed]
  • Bohman M. Some genetic aspects of alcoholism and criminality. A population of adoptees. Arch Gen Psychiatry. 1978 Mar;35(3):269–276. [PubMed]
  • Cloninger CR, Bohman M, Sigvardsson S. Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Arch Gen Psychiatry. 1981 Aug;38(8):861–868. [PubMed]

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