The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ADH1C  -  alcohol dehydrogenase 1C (class I), gamma...

Homo sapiens

Synonyms: ADH3, Alcohol dehydrogenase 1C, Alcohol dehydrogenase subunit gamma
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ADH1C

  • A rare truncating mutation in ADH1C (G78Stop) shows significant association with Parkinson disease in a large international sample [1].
  • We previously demonstrated that a functional polymorphism in alcohol dehydrogenase type 1C (ADH1C, also known as ADH3) modifies the association between moderate alcohol consumption and high-density lipoprotein (HDL) levels and risk of myocardial infarction among older men [2].
  • Therefore, the aim of the current study was to investigate possible associations of MCV value with polymorphisms of ADH1C in white patients with alcohol-associated esophageal carcinoma, chronic alcoholic pancreatitis, and alcoholic cirrhosis as well as in heavy drinkers without organ damage [3].
  • There was a significant interaction of alcohol use and genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1 (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI, 1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling for smoking, age, race, and gender) [4].
  • The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head and neck associated with alcohol and tobacco use [4].

Psychiatry related information on ADH1C

  • Our results confirm that ADH1C genotype modifies the association between alcohol consumption and HDL levels among men and postmenopausal women not using PMH who drink moderately [2].

High impact information on ADH1C

  • RESULTS: At 33 or 500 mmol/L ethanol, pH 7.5, the activities in the ADH3 1-1 phenotypic and mu-ADH-expressing mucosal specimens were significantly greater than that in the ADH3 1-2 phenotypic and mu-ADH absent mucosal specimens, respectively [5].
  • 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 [6].
  • Since ADH catalyzes the conversion of retinol to retinal, which can be further converted to retinoic acid by aldehyde dehydrogenase, these results suggest that retinoic acid activation of ADH3 constitutes a positive feedback loop regulating retinoic acid synthesis [7].
  • Deletion mapping experiments identified a region in the ADH3 promoter located between -328 and -272 bp which confers retinoic acid activation [7].
  • Within a 34-bp stretch, the ADH3 retinoic acid response element (RARE) contains two TGACC motifs and one TGAAC motif, both of which exist in RAREs controlling other genes [7].

Chemical compound and disease context of ADH1C

  • Kinetic simulations using the experimentally determined Hill constant suggest that gastric ADH3 may highly effectively contribute to the first-pass metabolism at 0.5-3 M ethanol, an attainable range in the gastric lumen during alcohol consumption [8].

Biological context of ADH1C


Anatomical context of ADH1C


Associations of ADH1C with chemical compounds

  • ADH1C allozymes were the major contributor at low ethanol (< 2 mM), whereas ADH1B3 the major form at higher levels (> 10 mM) in ADH1B*3 individuals [11].
  • A methylated upstream region of ADH1C achieved histone H3 hyperacetylation upon either 5-aza-dC or TSA treatment [16].
  • Trichostatin A treatment elevated expression of ADH1C [16].
  • Variations in the ADH1B and ADH1C genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism, although most data on this question come from Asian populations [17].
  • CONCLUSIONS: Because the ADH1C gene is involved in the metabolic pathways of many alcohols, we propose several hypotheses about the causal pathway, including ethanol oxidation activity and, more probably, retinol oxidation [18].

Regulatory relationships of ADH1C

  • This might explain why ADH3 is expressed at lower levels than ADH2 in the liver [19].

Other interactions of ADH1C

  • Case-control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results [20].
  • Allelic variation at alcohol metabolism genes ( ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population [10].
  • For organisms where multiple species-specific isoenzymes exist within a class, we recommend adding a capital letter after the Arabic number; i.e. ADH1A, ADH1B, and ADH1C for human alpha, beta, and gamma class I ADHs, respectively [21].
  • For gastric mucosal-alcohol clearance, the relative contributions of ADH1C allozymes and ADH4 were converse as ethanol concentration increased [11].
  • The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes [22].

Analytical, diagnostic and therapeutic context of ADH1C


  1. A rare truncating mutation in ADH1C (G78Stop) shows significant association with Parkinson disease in a large international sample. Buervenich, S., Carmine, A., Galter, D., Shahabi, H.N., Johnels, B., Holmberg, B., Ahlberg, J., Nissbrandt, H., Eerola, J., Hellström, O., Tienari, P.J., Matsuura, T., Ashizawa, T., Wüllner, U., Klockgether, T., Zimprich, A., Gasser, T., Hanson, M., Waseem, S., Singleton, A., McMahon, F.J., Anvret, M., Sydow, O., Olson, L. Arch. Neurol. (2005) [Pubmed]
  2. Alcohol consumption and high-density lipoprotein levels: the effect of ADH1C genotype, gender and menopausal status. Hines, L.M., Hunter, D.J., Stampfer, M.J., Spiegelman, D., Chu, N.F., Rifai, N., Hankinson, S.E., Rimm, E.B. Atherosclerosis (2005) [Pubmed]
  3. Mean corpuscular volume and ADH1C genotype in white patients with alcohol-associated diseases. Sun, L., König, I.R., Jacobs, A., Seitz, H.K., Junghanns, K., Wagner, T., Ludwig, D., Jacrobs, A., Homann, N. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  4. The ADH1C polymorphism modifies the risk of squamous cell carcinoma of the head and neck associated with alcohol and tobacco use. Peters, E.S., McClean, M.D., Liu, M., Eisen, E.A., Mueller, N., Kelsey, K.T. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  5. Human stomach alcohol and aldehyde dehydrogenases: comparison of expression pattern and activities in alimentary tract. Yin, S.J., Liao, C.S., Wu, C.W., Li, T.T., Chen, L.L., Lai, C.L., Tsao, T.Y. Gastroenterology (1997) [Pubmed]
  6. 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]
  7. 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]
  8. The metabolic role of human ADH3 functioning as ethanol dehydrogenase. Lee, S.L., Wang, M.F., Lee, A.I., Yin, S.J. FEBS Lett. (2003) [Pubmed]
  9. Distant HNF1 site as a master control for the human class I alcohol dehydrogenase gene expression. Su, J.S., Tsai, T.F., Chang, H.M., Chao, K.M., Su, T.S., Tsai, S.F. J. Biol. Chem. (2006) [Pubmed]
  10. Allelic variation at alcohol metabolism genes ( ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. Mulligan, C.J., Robin, R.W., Osier, M.V., Sambuughin, N., Goldfarb, L.G., Kittles, R.A., Hesselbrock, D., Goldman, D., Long, J.C. Hum. Genet. (2003) [Pubmed]
  11. Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism. Lee, S.L., Chau, G.Y., Yao, C.T., Wu, C.W., Yin, S.J. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  12. 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]
  13. Risk factors in alcohol associated breast cancer: alcohol dehydrogenase polymorphism and estrogens. Coutelle, C., Höhn, B., Benesova, M., Oneta, C.M., Quattrochi, P., Roth, H.J., Schmidt-Gayk, H., Schneeweiss, A., Bastert, G., Seitz, H.K. Int. J. Oncol. (2004) [Pubmed]
  14. Differential activity of the promoter for the human alcohol dehydrogenase (retinol dehydrogenase) gene ADH3 in neural tube of transgenic mouse embryos. Zgombić-Knight, M., Satre, M.A., Duester, G. J. Biol. Chem. (1994) [Pubmed]
  15. Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms. Coutelle, C., Ward, P.J., Fleury, B., Quattrocchi, P., Chambrin, H., Iron, A., Couzigou, P., Cassaigne, A. Hum. Genet. (1997) [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. Associations of variations in alcohol dehydrogenase genes with the level of response to alcohol in non-Asians. Duranceaux, N.C., Schuckit, M.A., Eng, M.Y., Robinson, S.K., Carr, L.G., Wall, T.L. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  18. Interaction between the ADH1C polymorphism and maternal alcohol intake in the risk of nonsyndromic oral clefts: an evaluation of the contribution of child and maternal genotypes. Chevrier, C., Perret, C., Bahuau, M., Nelva, A., Herman, C., Francannet, C., Robert-Gnansia, E., Cordier, S. Birth defects research. Part A, Clinical and molecular teratology. (2005) [Pubmed]
  19. 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]
  20. Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? Zintzaras, E., Stefanidis, I., Santos, M., Vidal, F. Hepatology (2006) [Pubmed]
  21. Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Duester, G., Farrés, J., Felder, M.R., Holmes, R.S., Höög, J.O., Parés, X., Plapp, B.V., Yin, S.J., Jörnvall, H. Biochem. Pharmacol. (1999) [Pubmed]
  22. Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians. Foley, P.F., Loh, E.W., Innes, D.J., Williams, S.M., Tannenberg, A.E., Harper, C.G., Dodd, P.R. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  23. Increased cancer risk in heavy drinkers with the alcohol dehydrogenase 1C*1 allele, possibly due to salivary acetaldehyde. Visapää, J.P., Götte, K., Benesova, M., Li, J., Homann, N., Conradt, C., Inoue, H., Tisch, M., Hörrmann, K., Väkeväinen, S., Salaspuro, M., Seitz, H.K. Gut (2004) [Pubmed]
  24. ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago. Montane-Jaime, K., Moore, S., Shafe, S., Joseph, R., Crooks, H., Carr, L., Ehlers, C.L. Alcohol (2006) [Pubmed]
  25. Improved methods for genotype determination of human alcohol dehydrogenase (ADH) at ADH 2 and ADH 3 loci by using polymerase chain reaction-directed mutagenesis. Groppi, A., Begueret, J., Iron, A. Clin. Chem. (1990) [Pubmed]
  26. Alcohol sensitivity in Taiwanese men with different alcohol and aldehyde dehydrogenase genotypes. Peng, G.S., Yin, J.H., Wang, M.F., Lee, J.T., Hsu, Y.D., Yin, S.J. J. Formos. Med. Assoc. (2002) [Pubmed]
  27. 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]
WikiGenes - Universities