Skip to main content
Log in

The contribution of polymorphism in the alcohol dehydrogenase β subunit to alcohol sensitivity in a Japanese population

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

In humans, ingested alcohol is mainly metabolized by the combination of class I alcohol dehydrogenase (ADII) and aldehyde dehydrogenase (ALDH). In Orientals, there are highly frequent polymorphisms both in the class I ADH β subunit (ADHZ) and in the low Km ALDH (ALDH2). We characterized the three genotypes of ALDH2 in a Japanese population. In the present study, we evaluated the effects of the ADH2 polymorphism in the same population (424 males and 100 females) controlling for the effects of the ALDH2 polymorphism. In the ALDH21/ALDH22 group, the frequency of facial flushing with one glass of beer was significantly higher in the ADH2 1/ADH2 2 and ADH2 2/ADH2 2 genotype than in the ADH2 1/ADH2 1 genotype. Likewise, the proportion of persons with positive results for ethanol-induced cutaneous erythema differed significantly depending on the ADH2 genotype in both the ALDH21/ALDH21 and ALDH21/ALDH22 genotypes. However, drinking habits were not significantly associated with the ADH2 genotype, suggesting that the ADH2 genotype influences the metabolism of ethanol only in the peripheral tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Agarwal DP, Goedde HW (1990a) Alcohol metabolism, alcohol intolerance, and alcoholism. Springer-Verlag, Berlin Heidelberg

    Google Scholar 

  • Agarwal DP, Goedde HW (1990b) Pharmacogenetics of alcohol dehydrogenase (ADH). Pharmacol Ther 45: 69–83

    Google Scholar 

  • Chao Y-C, Liou S-R, Chung Y-Y, Tang H-S, Hsu C-T, Li T-K, Yin S-J (1994) Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. Hepatology 19: 360–366

    Google Scholar 

  • Chen S-H, Zhang M, Wang N-S, Scott CR (1994) Gene frequencies of alcohol dehydrogenase2 (ADH2) and aldehyde dehydrogenase2 (ALDH2) in five Chinese minorities. Hum Genet 94: 571–572

    Google Scholar 

  • Duester G, Smith M, Bilanchone V, Hatfield GW (1986) Molecular analysis of the human class I alcohol dehydrogenase family and nucleotide sequence of the gene encoding the β subunit. J Biol Chem 261: 2027–2033

    Google Scholar 

  • Engeland K, Maret W (1993) Extrahepatic, differential expression of four classes of human alcohol dehydrogenase. Biochem Biophys Res Commun 193: 47–53

    Google Scholar 

  • Fukui M, Wakasugi C (1972) Liver alcohol dehydrogenase in a Japanese population. Jpn J Legal Med 26: 46–51

    Google Scholar 

  • Goedde HW, Agarwal DP, Harada S (1979a) Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. Clin Genet 16: 29–33

    Google Scholar 

  • Goedde HW, Harada S, Agarwal DP (1979b) Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet 51: 331–334

    Google Scholar 

  • Goedde HW, Agarwal DP, Fritze G, Meier-Tackmann D, Singh S, Beckmann G, Bhatia K, Chen LZ, Fang B, Liskar R, Paik YK, Rothhammer F, Saba N, Segal B, Srivastava LM, Czeizel A (1992) Distribution of ADH2 and ALDH2 genotypes in different populations. Hum Genet 88: 344–346

    Google Scholar 

  • Harada S, Misawa S, Agarwal DP, Goedde HW (1980) Liver alcohol and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. Am J Hum Genet 32: 8–15

    Google Scholar 

  • Harada S, Agarwal DP, Goedde HW (1981) Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet II: 982

    Google Scholar 

  • Higuchi S, Muramatsu T, Saito M, Sasao M, Maruyama K, Kono H, Niimi Y (1987) Ethanol patch test for low Km aldehyde dehydrogenase deficiency. Lancet 1: 629

    Google Scholar 

  • Ikuta T, Fujiyoshi T, Kurachi K, Yoshida A (1985) Molecular cloning of a full-length cDNA for human alcohol dehydrogenase. Proc Natl Acad Sci USA 82: 2703–2707

    Google Scholar 

  • Ikuta T, Szeto S, Yoshida A (1986) Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence. Proc Natl Acad Sci USA 83: 634–638

    Google Scholar 

  • Ikuta T, Shibuya A, Yoshida A (1988) Direct detection of usual (Caucasian-type) and atypical (Oriental-type) alleles of the class I human alcohol dehydrogenase-2 locus. Biochem Genet 26: 519–525

    Google Scholar 

  • Jörnvall H, Hempel J, Vallee BL, Boston WF, Li TK (1984) Human liver alcohol dehydrogenase: amino acid substitution in the β2β2 Oriental isozyme explains functional properties, establishes an active site structure, and parallels mutational exchanges in the yeast enzyme. Proc Natl Acad Sci USA 81: 3024–3028

    Google Scholar 

  • Nakamura K, Suwaki H, Matsuo Y, Ichikawa Y, Miyatake R, Iwahashi K (1995) Association between alcoholics and the genotypes of ALDH2, ADH2, ADH3 as well as P-4502E1. Jpn J Alcohol Drug Depend 30: 33–42

    Google Scholar 

  • Shibuya A, Yoshida A (1988) Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH2 1) with the disease. Am J Hum Genet 43: 744–748

    Google Scholar 

  • Smith M, Hopkinson DA, Harris H (1971) Developmental changes and polymorphism in human alcohol dehydrogenase. Ann Hum Genet 34: 251–271

    Google Scholar 

  • Smith M, Hopkinson DA, Harris H (1972) Alcohol dehydrogenase isozyme in adult human stomach and liver: evidence for activity of the ADH3 locus. Ann Hum Genet 35: 243

    Google Scholar 

  • Stamatoyannopoulos G, Chen SH, Fukui M (1975) Liver alcohol dehydrogenase in Japanese: high population frequency of atypical form and its possible role in alcohol sensitivity. Am J Hum Genet 27: 789–796

    Google Scholar 

  • Takeshita T, Morimoto K, Mao X, Hashimoto T, Furuyama J (1993) Phenotypic differences in low Km aldehyde dehydrogenase in Japanese workers. Lancet 341: 837–838

    Google Scholar 

  • Takeshita T, Morimoto K, Mao X, Hashimoto T, Furuyama J (1994) Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population. Hum Genet 94: 217–223

    Google Scholar 

  • Thomasson HR, Edenberg H J. Crabb DW, Mai X, Jerome RE, Li TK, Wang S, Lin Y, Lu R, Yin S (1991) Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am J Hum Genet 48: 677–681

    Google Scholar 

  • Wartburg JP von, Bühler R (1984) Alcoholism and aldehydism: new biomedical concepts. Lab Invest 50: 5–15

    Google Scholar 

  • Wartburg JP von, Schürch PM (1968) Atypical human liver alcohol dehydrogenase. Ann NY Acad Sci 151: 936–946

    Google Scholar 

  • Wartburg JP von, Papenberg J, Aebi H (1965) An atypical human alcohol dehydrogenase. Can J Biochem 43: 889–898

    Google Scholar 

  • Wilkin JK, Fortner G (1985) Cutaneous vascular sensitivity to lower aliphatic alcohols and aldehydes in Orientals. Alcohol Clin Exp Res 9: 522–525

    Google Scholar 

  • Wolff PH (1972) Ethnic differences in alcohol sensitivity. Science 175:449–450

    Google Scholar 

  • Wolff PH (1973) Vasomotor sensitivity to alcohol in diverse Mongoloid populations. Am J Hum Genet 25: 193–199

    Google Scholar 

  • Xu Y, Carr L, Bosron WF, Li TK, Edenberg HJ (1988) Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. Genomics 2: 209–214

    Google Scholar 

  • Yamada K, Asaka A, Norioka T, Takeshita T (1988) Questionnaire for detecting the phenotype of low Km ALDH (ALDH2). In: K Kuriyama, A Takada and H Ishii (eds) Biomedical and social aspects of alcohol and alcoholism. Elsevier, Amsterdam, pp 481–484

    Google Scholar 

  • Yamamoto K, Ueno Y, Mizoi Y, Tatsuno Y (1993) Genetic polymorphism of alcohol and aldehyde dehydrogenase and the effects on alcohol metabolism. Jpn J Alcohol Drug Depend 28: 13–25

    Google Scholar 

  • Yin SJ, Boston WF, Magnes LJ, Li TK (1984) Human liver alcohol dehydrogenase: purification and kinetic characteristics of the β2β2, β2β1, and β2γ1 “Oriental” isozymes. Biochemistry 23: 5847–5853

    Google Scholar 

  • Yoshida A, Impraim CC, Huang IY (1981) Enzymatic and structural differences between usual and atypical human livar alcohol dehydrogenases. J Biol Chem 256: 12430–12436

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takeshita, T., Mao, XQ. & Morimoto, K. The contribution of polymorphism in the alcohol dehydrogenase β subunit to alcohol sensitivity in a Japanese population. Hum Genet 97, 409–413 (1996). https://doi.org/10.1007/BF02267057

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02267057

Keywords

Navigation