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Enzymatic Aspects of Alcoholism-ADH and ALDH

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Textbook of Addiction Treatment: International Perspectives

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Abstract

Most ethanol taken into the body is converted to acetaldehyde by alcohol dehydrogenase (ADH), and then from acetaldehyde to acetic acid by aldehyde dehydrogenase (ALDH). However, polymorphisms exist in the genes of these enzymes. A super-active form of ADH1B and an inactive form of ALDH2 have preventive effects against alcoholism. In addition, several reports have suggested an association between polymorphisms in ADH1C, ADH4, and ALDH1A1 and alcoholism. Moderate to heavy drinkers with inactive ALDH2 and less-active ADH1B have a much higher risk of gastrointestinal tract cancer compared with those with active ALDH2 and super-active ADH1B. The ADH1B and ALDH2 polymorphisms are associated with various physical diseases such as liver disease, pancreatitis, and diabetes mellitus. Alcoholics with inactive ALDH2 have unique clinical characteristics; for example, they develop alcoholism more slowly. Inactive ALDH2 is thought to cause high blood acetaldehyde concentrations and a painful flushing response, which suppresses alcohol consumption. However, the mechanism by which super-active ADH1B decreases alcohol consumption and the risk of alcoholism remains unclear. Identifying ADH1B and ALDH2 genotypes might be useful in the prevention and treatment of alcoholism.

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References

  • Birley AJ, James MR, Dickson PA, Montgomery GW, Heath AC, Martin NG, Whitfield JB (2009) ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. Hum Mol Genet 18(8):1533–1542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boccia S, Hashibe M, Galli P, De Feo E, Asakage T, Hashimoto T, Hiraki A, Katoh T, Nomura T, Yokoyama A, van Duijn CM, Ricciardi G, Boffetta P (2009) Aldehyde dehydrogenase 2 and head and neck cancer: a meta-analysis implementing a Mendelian randomization approach. Cancer Epidemiol Biomarkers Prev 18(1):248–254

    Article  CAS  PubMed  Google Scholar 

  • Edenberg HJ, Xuei X, Chen HJ, Tian H, Wetherill LF, Dick DM, Almasy L, Bierut L, Bucholz KK, Goate A, Hesselbrock V, Kuperman S, Nurnberger J, Porjesz B, Rice J, Schuckit M, Tischfield J, Begleiter H, Foroud T (2006) Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet 15(9):1539–1549

    Article  CAS  PubMed  Google Scholar 

  • Ehlers CL, Spence JP, Wall TL, Gilder DA, Carr LG (2004) Association of ALDH1 promoter polymorphisms with alcohol-related phenotypes in southwest California Indians. Alcohol Clin Exp Res 28(10):1481–1486

    Article  CAS  PubMed  Google Scholar 

  • Eriksson CJ, Fukunaga T, Sarkola T, Chen WJ, Chen CC, Ju JM, Cheng AT, Yamamoto H, Kohlenberg-Muller K, Kimura M, Murayama M, Matsushita S, Kashima H, Higuchi S, Carr L, Viljoen D, Brooke L, Stewart T, Foroud T, Su J, Li TK, Whitfield JB (2001) Functional relevance of human adh polymorphism. Alcohol Clin Exp Res 25(5 Suppl ISBRA):157S–163S

    Article  CAS  PubMed  Google Scholar 

  • Gizer IR, Edenberg HJ, Gilder DA, Wilhelmsen KC, Ehlers CL (2011) Association of alcohol dehydrogenase genes with alcohol-related phenotypes in a Native American community sample. Alcohol Clin Exp Res 35(11):2008–2018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goedde HW, Agarwal DP, Fritze G, Meier-Tackmann D, Singh S, Beckmann G, Bhatia K, Chen LZ, Fang B, Lisker R et al (1992) Distribution of ADH2 and ALDH2 genotypes in different populations. Hum Genet 88(3):344–346

    Article  CAS  PubMed  Google Scholar 

  • Higuchi S, Matsushita S, Muramatsu T, Murayama M, Hayashida M (1996) Alcohol and aldehyde dehydrogenase genotypes and drinking behavior in Japanese. Alcohol Clin Exp Res 20(3):493–497

    Article  CAS  PubMed  Google Scholar 

  • Kimura M, Sawayama T, Matsushita S, Higuchi S, Kashima H (2009) Association between personality traits and ALDH2 polymorphism in Japanese male alcoholics. Alcohol Clin Exp Res 33(5):799–803

    Article  PubMed  Google Scholar 

  • Kimura M, Miyakawa T, Matsushita S, So M, Higuchi S (2011) Gender differences in the effects of ADH1B and ALDH2 polymorphisms on alcoholism. Alcohol Clin Exp Res 35(11):1923–1927

    Article  CAS  PubMed  Google Scholar 

  • Li D, Zhao H, Gelernter J (2011) Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases. Biol Psychiatry 70(6):504–512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li D, Zhao H, Gelernter J (2012) Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians. Hum Genet 131(5):725–737

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Long JC, Knowler WC, Hanson RL, Robin RW, Urbanek M, Moore E, Bennett PH, Goldman D (1998) Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population. Am J Med Genet 81(3):216–221

    Article  CAS  PubMed  Google Scholar 

  • Luu SU, Wang MF, Lin DL, Kao MH, Chen ML, Chiang CH, Pai L, Yin SJ (1995) Ethanol and acetaldehyde metabolism in chinese with different aldehyde dehydrogenase-2 genotypes. Proc Natl Sci Counc Repub China B 19(3):129–136

    CAS  PubMed  Google Scholar 

  • Mizoi Y, Yamamoto K, Ueno Y, Fukunaga T, Harada S (1994) Involvement of genetic polymorphism of alcohol and aldehyde dehydrogenases in individual variation of alcohol metabolism. Alcohol Alcohol 29(6):707–710

    CAS  PubMed  Google Scholar 

  • Montane-Jaime K, Moore S, Shafe S, Joseph R, Crooks H, Carr L, Ehlers CL (2006) ADH1C*2 allele is associated with alcohol dependence and elevated liver enzymes in Trinidad and Tobago. Alcohol 39(2):81–86

    Article  CAS  PubMed  Google Scholar 

  • Murayama M, Matsushita S, Muramatsu T, Higuchi S (1998) Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2. Alcohol Clin Exp Res 22(2):524–527

    Article  CAS  PubMed  Google Scholar 

  • Neumark YD, Friedlander Y, Durst R, Leitersdorf E, Jaffe D, Ramchandani VA, O’Connor S, Carr LG, Li TK (2004) Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. Alcohol Clin Exp Res 28(1):10–14

    Article  CAS  PubMed  Google Scholar 

  • Reich T, Edenberg HJ, Goate A, Williams JT, Rice JP, Van Eerdewegh P, Foroud T, Hesselbrock V, Schuckit MA, Bucholz K, Porjesz B, Li TK, Conneally PM, Nurnberger JI Jr, Tischfield JA, Crowe RR, Cloninger CR, Wu W, Shears S, Carr K, Crose C, Willig C, Begleiter H (1998) Genome-wide search for genes affecting the risk for alcohol dependence. Am J Med Genet 81(3):207–215

    Article  CAS  PubMed  Google Scholar 

  • Spence JP, Liang T, Eriksson CJ, Taylor RE, Wall TL, Ehlers CL, Carr LG (2003) Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations. Alcohol Clin Exp Res 27(9):1389–1394

    Article  CAS  PubMed  Google Scholar 

  • Suwaki H, Kalant H, Higuchi S, Crabbe JC, Ohkuma S, Katsura M, Yoshimura M, Stewart RC, Li TK, Weiss F (2001) Recent research on alcohol tolerance and dependence. Alcohol Clin Exp Res 25(5 Suppl ISBRA):189S–196S

    Article  CAS  PubMed  Google Scholar 

  • Thomasson HR, Beard JD, Li TK (1995) ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics. Alcohol Clin Exp Res 19(6):1494–1499

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama A, Kato H, Yokoyama T, Tsu**aka T, Muto M, Omori T, Haneda T, Kumagai Y, Igaki H, Yokoyama M, Watanabe H, Fukuda H, Yoshimizu H (2002) Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma. Carcinogenesis 23(11):1851–1859

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama A, Mizukami T, Matsui T, Yokoyama T, Kimura M, Matsushita S, Higuchi S, Maruyama K (2013) Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men. Alcohol Clin Exp Res 37:1394–1401

    Google Scholar 

  • Yoshida A (1994) Genetic polymorphisms of alcohol metabolizing enzymes related to alcohol sensitivity and alcoholic diseases. Alcohol Alcohol 29(6):693–696

    CAS  PubMed  Google Scholar 

  • Zintzaras E, Stefanidis I, Santos M, Vidal F (2006) Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? Hepatology 43(2):352–361

    Article  CAS  PubMed  Google Scholar 

Further Reading

  • Higuchi S, Matsushita S, Masaki T, Yokoyama A, Kimura M, Suzuki G, Mochizuki H (2004) Influence of genetic variations of ethanol-metabolizing enzymes on phenotypes of alcohol-related disorders. Ann N Y Acad Sci 1025:472–480

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama A, Omori T, Yokoyama T (2010) Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians. Keio J Med 59(4):115–130

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. National Hospital Organization, Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan

    Mitsuru Kimura, Akira Yokoyama, Sachio Matsushita & Susumu Higuchi

Authors
  1. Mitsuru Kimura
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  2. Akira Yokoyama
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  3. Sachio Matsushita
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  4. Susumu Higuchi
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Corresponding author

Correspondence to Mitsuru Kimura .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Alberta Gambling Research Institute University of Calgary, Calgary, Alberta, Canada

    Nady el-Guebaly

  2. Faculty of Brain Sciences UCL Division of Psychiatry, University College London, London, United Kingdom

    Giuseppe Carrà

  3. Division of Alcoholism & Drug Abuse, New York University School of Medicine, New York, New York, USA

    Marc Galanter

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Kimura, M., Yokoyama, A., Matsushita, S., Higuchi, S. (2015). Enzymatic Aspects of Alcoholism-ADH and ALDH. In: el-Guebaly, N., Carrà, G., Galanter, M. (eds) Textbook of Addiction Treatment: International Perspectives. Springer, Milano. https://doi.org/10.1007/978-88-470-5322-9_13

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  • DOI: https://doi.org/10.1007/978-88-470-5322-9_13

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  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-5321-2

  • Online ISBN: 978-88-470-5322-9

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