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.
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Agarwal DP, Goedde HW (1990a) Alcohol metabolism, alcohol intolerance, and alcoholism. Springer-Verlag, Berlin Heidelberg
Agarwal DP, Goedde HW (1990b) Pharmacogenetics of alcohol dehydrogenase (ADH). Pharmacol Ther 45: 69–83
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
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
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
Engeland K, Maret W (1993) Extrahepatic, differential expression of four classes of human alcohol dehydrogenase. Biochem Biophys Res Commun 193: 47–53
Fukui M, Wakasugi C (1972) Liver alcohol dehydrogenase in a Japanese population. Jpn J Legal Med 26: 46–51
Goedde HW, Agarwal DP, Harada S (1979a) Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. Clin Genet 16: 29–33
Goedde HW, Harada S, Agarwal DP (1979b) Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet 51: 331–334
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
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
Harada S, Agarwal DP, Goedde HW (1981) Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet II: 982
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
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
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
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
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
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
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
Smith M, Hopkinson DA, Harris H (1971) Developmental changes and polymorphism in human alcohol dehydrogenase. Ann Hum Genet 34: 251–271
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
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
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
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
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
Wartburg JP von, Bühler R (1984) Alcoholism and aldehydism: new biomedical concepts. Lab Invest 50: 5–15
Wartburg JP von, Schürch PM (1968) Atypical human liver alcohol dehydrogenase. Ann NY Acad Sci 151: 936–946
Wartburg JP von, Papenberg J, Aebi H (1965) An atypical human alcohol dehydrogenase. Can J Biochem 43: 889–898
Wilkin JK, Fortner G (1985) Cutaneous vascular sensitivity to lower aliphatic alcohols and aldehydes in Orientals. Alcohol Clin Exp Res 9: 522–525
Wolff PH (1972) Ethnic differences in alcohol sensitivity. Science 175:449–450
Wolff PH (1973) Vasomotor sensitivity to alcohol in diverse Mongoloid populations. Am J Hum Genet 25: 193–199
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
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
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
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
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
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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
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DOI: https://doi.org/10.1007/BF02267057