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Genetic Basis of Idiosyncratic Responses to Alcoholism
European Journal of Clinical and Biomedical Sciences
Volume 2, Issue 6, December 2016, Pages: 63-68
Received: Oct. 7, 2016; Accepted: Nov. 11, 2016; Published: Dec. 12, 2016
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Charles Ejike Osuji, Biotechnology Advanced Research Center, Sheda Science and Technology Complex (SHESTCO), Abuja, Nigeria
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Aim: The scientific viewpoint of genetic polymorphisms associated with risk of alcoholism and its adverse individual behavioural reactions is the main focus of this review. A complex syndrome like alcoholism and its idiosyncrasy may not be entirely understood on the basis of pathophysiological concept of neurotransmission alone. While neuropharmacology explains the mechanism behind molecular basis of alcoholism, the variation in alcohol induced abnormal neurotransmission due to presence or absence of different gene variants or isoenzymes of a particular gene on the other hand is a strong indication of genetic predisposition to alcoholism. In this article the term alcohol is used as a generic name for ethanol, which is the main subject of this discussion. Conclusion: The concomitant untoward intrinsic toxicity associated with alcoholism that makes it a potential trigger to a myriad of abnormal behavioural reactions in not only dose dependent pattern but with strong genetic disposition arises majorly due to different modes and levels of genetic variation in metabolic enzymes.
Alcoholism, Genetic, Polymorphism Neurotransmission, Enzymes, ALDH, ADH, Cytochrome P450
To cite this article
Charles Ejike Osuji, Genetic Basis of Idiosyncratic Responses to Alcoholism, European Journal of Clinical and Biomedical Sciences. Vol. 2, No. 6, 2016, pp. 63-68. doi: 10.11648/j.ejcbs.20160206.12
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
McGovern 2009; McGovern, P. Uncorking the Past: The Quest for Wine, Beer, and Other Alcoholic Beverages. Berkley; Los Angeles; London: The Regents of the University of California, 2009.
Tramacere et al. 2012b, c). Tramacere, I.; Pelucchi, C.; Bonifazi, M.; et al. A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma. European Journal of Cancer Prevention 21(3): 268–273, 2012b.
Volume of World Beer Production. European Beer Guide. Archived from the original 2006. European Beerguide. net.
Nelson, Max. The Barbarian’s Beverage; A History of Beer in Ancient Europe. Abingdon, Oxon: Routledge. 2005 p. 1. ISBN 0-415-31121-7.
Rudgley, Richard. The Alchemy of culture. Intoxicanys in the society. London: British Museum Press. 1993; p. 411. ISBN 978-0-7141-1736-2.
Arnold, John P. Origin and History of Beer Brewing. From Prehistoric Times to the Begining of Brewing Science and Technology. Cleveland, Ohio: Reprint Edition by BeerBooks. 2005; p. 411. ISBN 0-9662084-1-2.
Joshua J. Mark. Beer. Ancient History Encyclopedia. 2011.
Google Books. World’s Best Beers 2009. ISBN 978-1-4027-6694-7.
Kevin D. Shield, Charles, Parry and Jürgen Rehm. Chronic Diseases and Conditions Related to Alcohol Use. Alcohol research; current reviews 2013 vol. 35 No 2.
[10] Alcohol intoxication
Brain & Mind Magazine. An Initiative by the Centre for Biomedical Informatics; 3 (8) 1999.
Rehm J, Room R, Graham K, Monteiro M, Gmel G, Sempos CT: The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease: an overview. Addiction. 2003, 98: 1209-1228.10.1046/j.1360- 43.2003.00467.
Sulik KK: Genesis of alcohol-induced craniofacial dysmorphism. Exp Biol Med. 2005, 230: 366-375
Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012 Mar; 73(3): 348–362. Published online 2011 Oct 11. doi: 10.1111/j.1365-2125.2011.04111.
Thomasson HR, Crabb DW, Edenberg HJ, Li TK: Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behav Genet. 1993, 23: 131-136. 10.1007/BF01067417.
Hendershot CS, Lindgren KP, Liang T, Hutchison KE: COMT and ALDH2 polymorphisms moderate associations of implicit drinking motives with alcohol use. Addict Biol. 2011, 17: 192-201.
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: Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet. 2006, 15: 1539-1549. 10.1093.
Goldman D, Oroszi G, Ducci F: The genetics of addictions: uncovering the genes. at. Rev Genet. 2005, 6: 521-532.
Carl, Sherman., Impacts of Drugs on Neurotransmission; NIDA 2007.
Yingmei Zhang and Jun Ren -ALDH2 in Alcoholic Heart Diseases: Molecular Mechanism and Clinical Implications. doi: 10.1016/j.pharmthera.2011.05.008.
Pohorecky, L. A. Biphasic action of ethanol. Biobehavioral Reviews 1: 231–240, 1977. Shepherd, G. M. Neurobiology. 3d ed. New York: Oxford University Press, 1994.
Tabakoff, B., and Hoffman, P. L. Alcohol addiction: An enigma among us. Neuron. 1996 16: 909–912.
Valenzuela, C. F., and Harris, R. A. Alcohol: Neurobiology. In: Lowinson, J. H.; Ruiz, P.; Millman, R. B.; and Langrod, J. G., eds. Substance Abuse: A Comprehensive Textbook. Baltimore: Williams & Wilkins, 1997. pp. 119–142.
Ramchandani, V. A.; O’Connor, S.; Neumark, Y. D.; et al. The alcohol clamp: Applications, challenges and new directions. Alcoholism: Clinical and Experimental Research. 2006; 30: 155–164.
O’Connor, S.; Morzorati, S., Christian, J.; and Li, T.-K. Clamping breath alcohol concentration reduces experimental variance: Application to the study of acute tolerance to alcohol and alcohol elimination rate. Alcoholism: Clinical and Experimental Research 1998; 22: 202–210.
Alcohol Research & Health, Vol. 30, No. 1, 2007.
Martin, N. G.; Perl, J.; Oakeshott, J. G.; Gibson, J. B.; Starmer, G. A.; and Wilks, A. V. A twin study of ethanol metabolism. Behavioural Genetics. 1985; 15: 93–109.
Zucker RA, Kincaid SB, Fitzgerald HE, Bingham CR. Alcohol schema acquisition in preschoolers: Differences between children of alcoholics and children of nonalcoholics. Alcoholism: Clinical and Experimental Research. 1995; 19: 1011– 1017.
Ron Weathermon, and David W. Crabb. Alcohol and Medication Interactions. 1999 Vol. 23, No. 1.
Tatiana V Morozova and David Goldman, The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks 2012.
Hurley, T. D.; Edenberg, H. J.; Li, T.-K. The Pharmacogenomics of alcoholism. In: Pharmacogenomics: The Search for Individualized Therapies. Weinheim, Germany: Wiley–VCH, 2002, pp. 417–441.
Thompson, R. F. The Brain: A Neuroscience Primer. New York: Worth Publishers 2000.
Merikangas KR. The genetic epidemiology of alcoholism. Psychological Medicine 1990; 20: 1122.
Pickens RW, Svikis DS, McGue M, Lykken D, Heston M, Clayton P. 1991. Heterogeneity in the inheritance of alcoholism: A study of male and female twins. Archives of General Psychiatry 48: 19-28.
Cadoret RJ, Cain C, Grove W. 1980. Development of alcoholism in adoptees raised apart from alcoholic biologic relatives. Archives cf General Psychiatry 37: 561-563.
Grove W, Eckert E, Heston L, Bouchard T, Segal N, Lykken D. 1990. Heritability of substance abuse and antisocial behavior: A study of monozygotic twins reared apart. Biological Psychiatry 27: 1293-1304.
Goodwin, Donald W. "Heredity" Alcoholism the facts. New York: Oxford University Press.
Whitfield, John B. "Genes for Alcohol Metabolism and Alcohol Sensitivity Their Role in the Genetics of Alcohol Dependence" Alcohol in Health and Disease. New York: Marcel Dekker, Inc., 2001.
Research Institute on Addictions, Washington Post, 1998.
Morse, RM; Flavin, DK. The definition of alcoholism, The joint committee of the national council on Alcoholism and Drug dependence and The American Society of Addiction Medicine to study the the definition and criteria for diagnosis of Alcoholism”. The Journal of the American Medical Association. 1992 268 (8): 1012. doi: 10.1001/jama..03490080086030.
Carlson, Neil R.; Buskist, William; Enzle, Michael E.; Heth, C. Donald. Psychology: The Science of Behaviour 3rd Canadian Edition. Pearson. 2005. pp. 75–76. ISBN 0-205-45769.
Luo X, Kranzler HR, Zuo L, Wang S, Blumberg HP, Gelernter J: CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study. Hum Mol Genet. 2005.
Ehringer MA, Clegg HV, Collins AC, Corley RP, Crowley T, Hewitt JK, Hopfer CJ, Krauter K, Lessem J, Rhee SH, et al. Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. Am J Med Genet B Neuropsychiatr Genet. 2007; 144B(5): 596–604. doi: 10.1002/ajmg.b.3046444.
Agrawal A, Edenberg HJ, Foroud T, Bierut LJ, Dunne G, Hinrichs AL, Nurnberger JI, Crowe R, Kuperman S, Schuckit MA, et al. Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample. Behav Genet. 2006; 36(5): 640–650. doi: 10.1007/s10519-006-9069-4.
Chen AC, Tang Y, Rangaswamy M, Wang JC, Almasy L, Foroud T, Edenberg HJ, Hesselbrock V, Nurnberger J, Jr, Kuperman S, et al. Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet. 2009; 150B(3): 359–368. doi: 10.1002/ajmg.b.30818.
Van Der Zwaluw CS, Engels RC, Vermulst AA, Rose RJ, Verkes RJ, Buitelaar J, Franke B, Scholte RH: A serotonin transporter polymorphism (5-HTTLPR) predicts the development of adolescent alcohol use. Drug Alcohol Depend. 2010, 112: 134-139. 10.1016/j.drugalcdep.2010.06.001.
Cao J, LaRocque E, Li D. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse. Am J Med Genet B Neuropsychiatr Genet. 2013; 162B(2): 169–176. doi: 10.1002/ajmg.b.32128.
Kohnke MD, Batra A, Kolb W, Kohnke AM, Lutz U, Schick S, Gaertner I. Association of the dopamine transporter gene with alcoholism. 2005; 40(5): 339–342. doi: 10.1093/alcalc/agh179.
Ashenhurst JR, Bujarski S, Ray LA. Delta and kappa opioid receptor polymorphisms influence the effects of naltrexone on subjective responses to alcohol. Pharmacol Biochem Behav. 2012; 103(2): 253–259. doi: 10.1016/j.pbb.2012.08.019.
Biological Factors Influence Alcohol. The Alcohol Pharmacology Education Partnership is powered by Word Press at Duke Word Press. The ABCs of Intoxication » Content: Biological Factors Influence Alcohol Intoxication Pt. 2.
Alcohol Metabolism: An Update. Alcohol Alert. National institute of alcohol abuse and alcoholism (NIAAA publication) 2007.
Thomasson, H. R.; Beard, J. D.; and Li, T. K. ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics. Alcoholism: Clinical and Experimental Research 19: 1494–1499, 1995.
Wall, T. L.; Garcia-Andrade, C.; Thomasson, H. R.; et al. Alcohol elimination in Native American Mission Indians: An investigation of interindividual variation. Alcoholism: Clinical and Experimental Research 20: 1159–1164, 1996.
Neumark, Y.; Friedlander, Y.; O’Connor, S.; et al. The influence of alcohol dehydrogenase polymorphisms on alcohol metabolism among Jewish males in Israel (Abstract). Alcoholism: Clinical and Experimental Research 2001; 25: 126A, 2001.
Edenberg HJ. Genetics of alcohol use disorders. In: Miller PM, editor. Biological research on addiction. London: Elsevier Science & Technology Books/Academic Press; 2013. pp. 500–508.
Rivera-Meza M, Quintanilla ME, Tampier L. Reduction of ethanol consumption in alcohol-preferring rats by dual expression gene transfer. Alcohol Alcohol. 2012; 47(2): 102–108. doi: 10.1093/alcalc/agr161.
Curtis, G. Steinmetz, Peiguang Xie, henry Weiner, Thomas D. Hurley. Structure of mitochondrial aldehyde dehydrogenase: The genetic component of ethanol aversion. 1997 DOI: 10.1016/S0969-2126(97)00224-4.
Mulligan CJ, Robin RW, Osier MV, Sambuughin N, Goldfarb LG, Kittles RA, Hesselbrock D, Goldman D, Long JC. Allelic variation at alcohol metabolism genes (ADH1B, ADH1C, ALDH2) and alcohol dependence in an American Indian population. Hum Genet. 2003; 113(4): 325–336. doi: 10.1007/s00439-003-0971-z.
Birley AJ, James MR, Dickson PA, Montgomery GW, Heath AC, Martin NG, Whitfield JB. Adh snp associations with alcohol metabolism in vivo. Hum Mol Genet. 2009; 8(8): 1533–1542. doi: 10.1093/hmg/ddp060.
Bierut LJ, Goate AM, Breslau N, Johnson EO, Bertelsen S, Fox L, Agrawal A, Bucholz KK, Grucza R, Hesselbrock V. ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. Mol. Psychiatry. 2012; 17(4): 445–450. doi: 10.1038/mp.2011.124.
Hurley TD, Edenberg HJ. Genes encoding enzymes involved in ethanol metabolism. Alcohol Res.2012; 34(3): 339–344.
Ehlers, C. L.; Gilder, D. A.; Harris L.; and Carr L. Association of the ADH2*3 allele with a negative family history of alcoholism in African American young adults. Alcoholism: Clinical and Experimental Research 25: 1773–1777, 2001.
Crabb, D. W. Ethanol oxidizing enzymes: Roles in alcohol metabolism and alcoholic liver disease. Progress in Liver Disease Progress in Liver Disease 13: 151–172, 1995.
KA Wafford, DM Burnett, TV Dunwiddie, RA Harris. Genetic differences in the ethanol sensitivity of GABAA receptors expressed in Xenopus oocytes, 1990.
Marco Catalano. Functionally gene linked polymorphic regions and genetically controlled neurotransmitters metabolism. The impact of genomic studies on neuropsychopharmacology Volume 11, Issue 6 2001.
Roland D. Ciaranello and Richard E. Boeh Genetic regulation of neurotransmitter enzymes and receptors: Relationship to the inheritance of psychiatric disorders Volume 12, Issue 1 1982; pp 11–35; doi: 10.1007/BF01065738.
Arqam Qayyum, Clement C. Zai Yuko Hirat, Arun K. Tiwari Sheraz Cheema Behdin Nowrouzi, Joseph H. Beitchman, and James L. Kennedy current neuropharmacology The Role of the Catechol-o-methyltransferase (COMT) Gene Val158Met in Aggressive Behavior, A Review of Genetic Studies 2015. doi: 10.2174/1570159X13666150612225836.
[68]; COMT catechol-O-methyltransferase Homo sapiens (human). updated sept 2016.
Von Knorring AL, Bohman M, von Knorring L, Oreland L. Platelet MAO activity as a biological marker in subgroups of alcoholism. Acta Psychiatrica Scandinavica 1985. 72(52): 51-58.
Pandey GN, Fawcett J, Gibbons R, Clark DC, Davis JM. Platelet monoamine oxidase in alcoholism. Biologic Psychiatry 1988. 24: 15-24.
Tabakoff B, Hoffman PL, Lee JM, Saito T, Willard B, De Leon-Jones F. Differences in platelet enzyme activity between alcoholics and nonalcoholics. New England Journal of Medicine 1988; 318: 134-139 Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007; 30(1): 5–13.
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