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Gene Review

ADH1B  -  alcohol dehydrogenase 1B (class I), beta...

Homo sapiens

Synonyms: ADH2, Alcohol dehydrogenase 1B, Alcohol dehydrogenase subunit beta, HEL-S-117
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Disease relevance of ADH1B


Psychiatry related information on ADH1B


High impact information on ADH1B

  • The complete sequence of 340 kb of DNA around the rice Adh1-adh2 region reveals interrupted colinearity with maize chromosome 4 [9].
  • In contrast, all of the factors bound to the 5'-flanking region of Adh2 are constitutively present and unchanged by hypoxia [10].
  • The transcriptional activation of maize alcohol dehydrogenase-1 (Adh1) and alcohol dehydrogenase-2 (Adh2) is accompanied by changes in the chromatin structure within the 5'-flanking region of each gene [10].
  • The ADH1B Arg47His functional polymorphism has the highest F(st) of the 54 SNPs in the ADH cluster, and it is significantly above the mean F(st) of 382 presumably neutral sites tested on the same 42 population samples [11].
  • Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium [12].

Chemical compound and disease context of ADH1B


Biological context of ADH1B


Anatomical context of ADH1B

  • Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms [15].
  • Therefore, we determined the genotypes of the ADH2, ADH3, and ALDH2 loci of alcoholic and nonalcoholic Chinese men living in Taiwan, using leukocyte DNA amplified by the PCR and allele-specific oligonucleotides [18].
  • ADH2 promoter DNA fragments containing various lengths of 5'-flanking sequences were fused upstream from the gene encoding chloramphenicol acetyltransferase (cat) and transfected into the HepG2 human hepatoma cell line [19].
  • While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2) [20].
  • The influences of estimated body water, recent drinking history, recent smoking history, polymorphism at the ADH2 and ADH3 loci, family history of alcoholism, and percentage Native American heritage on alcohol elimination rate were determined using multiple regression analyses [21].

Associations of ADH1B with chemical compounds

  • H3 histones associated with a methylated upstream region of ADH1B were hyperacetylated in TSA-treated, but not in 5-aza-dC-treated, HepG2 cells [16].
  • Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism [22].
  • The human ADH1A, ADH1B, and ADH1C genes encode alcohol dehydrogenases (ADHs) that metabolize ethanol [23].
  • By these criteria, all-trans-retinol, 4-oxo-retinol, and 4-hydroxy-retinol were successfully docked to both ADH1B and ADH4 [24].
  • The crystal structures of human ADH1B and ADH4 provide the opportunity to examine their active sites for potential binding to many diverse retinol structures using molecular docking algorithms [24].

Regulatory relationships of ADH1B

  • However, the ADH2 genotype did not seem to influence drinking frequency or amounts of alcohol intake in each ALDH2 genotype [25].
  • This might explain why ADH3 is expressed at lower levels than ADH2 in the liver [26].

Other interactions of ADH1B


Analytical, diagnostic and therapeutic context of ADH1B

  • Self reports of flushing reaction after drinking, cutaneous sensitivity to alcohol (patch test), and genotypic determination of ADH2, ADH3, and ALDH2 were studied in 53 Brazilian volunteers of different ethnic groups [31].
  • In this study, we increased the sample size to investigate the modifying effect of lifetime alcohol consumption on the association between ADH1B and ALDH2 genotypes and the risks of esophageal cancer [13].
  • STUDY DESIGN: Blood samples from 263 black mother/child pairs (217 mothers and 239 children) were analyzed to determine incidence of the ADH1B allele and the relation of the maternal allele to pregnancy drinking assessed at every prenatal clinic visit [32].
  • No significant difference between the patient and control groups was found in the ADH2 genotypes [33].
  • Extracts from the primary root or scutellum of induced F2 seedlings from the above crosses were assayed for ADH activity by native polyacrylamide gel electrophoresis (PAGE) and simultaneously scored for survival to determine whether Adh2 and atn were segregating independently [34].


  1. Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking, smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma. Asakage, T., Yokoyama, A., Haneda, T., Yamazaki, M., Muto, M., Yokoyama, T., Kato, H., Igaki, H., Tsujinaka, T., Kumagai, Y., Yokoyama, M., Omori, T., Watanabe, H. Carcinogenesis (2007) [Pubmed]
  2. Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case-control study. Lilla, C., Koehler, T., Kropp, S., Wang-Gohrke, S., Chang-Claude, J. Br. J. Cancer (2005) [Pubmed]
  3. The contribution of polymorphism in the alcohol dehydrogenase beta subunit to alcohol sensitivity in a Japanese population. Takeshita, T., Mao, X.Q., Morimoto, K. Hum. Genet. (1996) [Pubmed]
  4. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility. Hori, H., Kawano, T., Endo, M., Yuasa, Y. J. Clin. Gastroenterol. (1997) [Pubmed]
  5. Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: implications for regulation of retinoic acid synthesis. Duester, G., Shean, M.L., McBride, M.S., Stewart, M.J. Mol. Cell. Biol. (1991) [Pubmed]
  6. No alcoholism-protection effects of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan. Lu, R.B., Ko, H.C., Lee, J.F., Lin, W.W., Huang, S.Y., Wang, T.J., Wu, Y.S., Lu, T.E., Chou, Y.H. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  7. Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers. Yokoyama, A., Omori, T. Jpn. J. Clin. Oncol. (2003) [Pubmed]
  8. ALDH2 status and conduct disorder mediate the relationship between ethnicity and alcohol dependence in Chinese, Korean, and White American college students. Luczak, S.E., Wall, T.L., Cook, T.A., Shea, S.H., Carr, L.G. Journal of abnormal psychology. (2004) [Pubmed]
  9. The complete sequence of 340 kb of DNA around the rice Adh1-adh2 region reveals interrupted colinearity with maize chromosome 4. Tarchini, R., Biddle, P., Wineland, R., Tingey, S., Rafalski, A. Plant Cell (2000) [Pubmed]
  10. In vivo footprinting reveals unique cis-elements and different modes of hypoxic induction in maize Adh1 and Adh2. Paul, A.L., Ferl, R.J. Plant Cell (1991) [Pubmed]
  11. Evidence of Positive Selection on a Class I ADH Locus. Han, Y., Gu, S., Oota, H., Osier, M.V., Pakstis, A.J., Speed, W.C., Kidd, J.R., Kidd, K.K. Am. J. Hum. Genet. (2007) [Pubmed]
  12. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Osier, M.V., Pakstis, A.J., Soodyall, H., Comas, D., Goldman, D., Odunsi, A., Okonofua, F., Parnas, J., Schulz, L.O., Bertranpetit, J., Bonne-Tamir, B., Lu, R.B., Kidd, J.R., Kidd, K.K. Am. J. Hum. Genet. (2002) [Pubmed]
  13. Interactive effects of lifetime alcohol consumption and alcohol and aldehyde dehydrogenase polymorphisms on esophageal cancer risks. Chen, Y.J., Chen, C., Wu, D.C., Lee, C.H., Wu, C.I., Lee, J.M., Goan, Y.G., Huang, S.P., Lin, C.C., Li, T.C., Chou, Y.P., Wu, M.T. Int. J. Cancer (2006) [Pubmed]
  14. Association of alcohol dehydrogenase 2*1 allele with liver damage and insulin concentration in the Japanese. Suzuki, Y., Ando, F., Ohsawa, I., Shimokata, H., Ohta, S. J. Hum. Genet. (2006) [Pubmed]
  15. Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms. Ishikawa, H., Ishikawa, T., Yamamoto, H., Fukao, A., Yokoyama, K. Mutat. Res. (2007) [Pubmed]
  16. Differential regulation of the alcohol dehydrogenase 1B (ADH1B) and ADH1C genes by DNA methylation and histone deacetylation. Dannenberg, L.O., Chen, H.J., Tian, H., Edenberg, H.J. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  17. Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci. Birley, A.J., Whitfield, J.B., Neale, M.C., Duffy, D.L., Heath, A.C., Boomsma, D.I., Martin, N.G. Behav. Genet. (2005) [Pubmed]
  18. Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Thomasson, H.R., Edenberg, H.J., Crabb, D.W., Mai, X.L., Jerome, R.E., Li, T.K., Wang, S.P., Lin, Y.T., Lu, R.B., Yin, S.J. Am. J. Hum. Genet. (1991) [Pubmed]
  19. A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites. Winter, L.A., Stewart, M.J., Shean, M.L., Dong, Y., Poellinger, L., Okret, S., Gustafsson, J.A., Duester, G. Gene (1990) [Pubmed]
  20. Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. Goedde, H.W., Agarwal, D.P., Harada, S. Clin. Genet. (1979) [Pubmed]
  21. Alcohol elimination in Native American Mission Indians: an investigation of interindividual variation. Wall, T.L., Garcia-Andrade, C., Thomasson, H.R., Cole, M., Ehlers, C.L. Alcohol. Clin. Exp. Res. (1996) [Pubmed]
  22. Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Huang, S.Y., Lin, W.W., Ko, H.C., Lee, J.F., Wang, T.J., Chou, Y.H., Yin, S.J., Lu, R.B. Alcohol. Clin. Exp. Res. (2004) [Pubmed]
  23. A retroviral repetitive element confers tissue-specificity to the human alcohol dehydrogenase 1C (ADH1C) gene. Chen, H.J., Carr, K., Jerome, R.E., Edenberg, H.J. DNA Cell Biol. (2002) [Pubmed]
  24. Molecular docking studies on interaction of diverse retinol structures with human alcohol dehydrogenases predict a broad role in retinoid ligand synthesis. Foglio, M.H., Duester, G. Biochim. Biophys. Acta (1999) [Pubmed]
  25. Association of the ADH2 genotypes with skin responses after ethanol exposure in Japanese male university students. Takeshita, T., Yang, X., Morimoto, K. Alcohol. Clin. Exp. Res. (2001) [Pubmed]
  26. Expression of the human ADH2 gene: an unusual Sp1-binding site in the promoter of a gene expressed at high levels in liver. Brown, C.J., Baltz, K.A., Edenberg, H.J. Gene (1992) [Pubmed]
  27. Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians. Luczak, S.E., Glatt, S.J., Wall, T.J. Psychological bulletin. (2006) [Pubmed]
  28. Considerable haplotype diversity within the 23kb encompassing the ADH7 gene. Han, Y., Oota, H., Osier, M.V., Pakstis, A.J., Speed, W.C., Odunsi, A., Okonofua, F., Kajuna, S.L., Karoma, N.J., Kungulilo, S., Grigorenko, E., Zhukova, O.V., Bonne-Tamir, B., Lu, R.B., Parnas, J., Schulz, L.O., Kidd, J.R., Kidd, K.K. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  29. Evaluation in vinyl chloride monomer-exposed workers and the relationship between liver lesions and gene polymorphisms of metabolic enzymes. Zhu, S.M., Ren, X.F., Wan, J.X., Xia, Z.L. World J. Gastroenterol. (2005) [Pubmed]
  30. Human stomach alcohol and aldehyde dehydrogenases (ALDH): a genetic model proposed for ALDH III isozymes. Yin, S.J., Cheng, T.C., Chang, C.P., Chen, Y.J., Chao, Y.C., Tang, H.S., Chang, T.M., Wu, C.W. Biochem. Genet. (1988) [Pubmed]
  31. Alcohol flushing, patch test, and ADH and ALDH genotypes in Brazilian ethnic groups. Santos, B.R., Monteiro, M.G., Walzer, C., Turler, H., Balant, L., von-Wartburg, J.P. Braz. J. Med. Biol. Res. (1995) [Pubmed]
  32. Protective effects of the alcohol dehydrogenase-ADH1B allele in children exposed to alcohol during pregnancy. Jacobson, S.W., Carr, L.G., Croxford, J., Sokol, R.J., Li, T.K., Jacobson, J.L. J. Pediatr. (2006) [Pubmed]
  33. Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease. Shibuya, A., Yoshida, A. Am. J. Hum. Genet. (1988) [Pubmed]
  34. Anaerobic tolerant null: a mutant that allows Adh1 nulls to survive anaerobic treatment. Lemke-Keyes, C.A., Sachs, M.M. J. Hered. (1989) [Pubmed]
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