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Gender Differences in Alcohol Metabolizing Hepatic Enzyme Genotypes in Korean Patients with Alcohol Dependence

Jin-Seong Lee / Sung-Gon Kim
  • Department of Psychiatry, Pusan National University Yangsan Hospital, Yangsan, Korea
  • Department of Psychiatry, School of Medicine, Pusan National University, Yangsan, Korea
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/ Sae-Heon Jang / Won-Tan Byun / In-Bok Hwang / Chang-Soo Kim / Seong-Yeon Kim / Hyun-Sook Lee / Young-Hui Yang / David W. Oslin
  • Department of Psychiatry, University of Pennsylvania, Philadelphia, PA and the Philadelphia VA Medical Center and VISN 4 MIRECC, USA
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Published Online: 2013-05-10 | DOI: https://doi.org/10.2478/addge-2013-0001


There are a number of epidemiological studies concerning the gender differences in the genetic etiology of alcohol dependence (AD), with ADH2 and ALDH2 being strong candidates. The purpose of this study was to investigate gender differences in frequencies of ADH2 and ALDH2 genotypes in AD patients and in a normal control (NC) group of Koreans. Study subjects consisted of 228 AD patients (180 males, 48 females) and 138 NC (79 males, 59 females). For both male and female subjects, the frequency of the ADH2*1/1 genotype was significantly higher in AD patients compared to the NC group. However, the effect size of the ADH2*1/1 genotype on AD was much larger in females than in males. Furthermore, the ALDH2*1/1 genotype was positively associated with AD in male subjects but negatively associated with AD in female patients. Interestingly, AD in males was primarily determined by ALDH2 enzyme activity (92%), whereas female AD was primarily determined by ADH2 enzyme activity (60.4%). These results suggest that risk for the development of AD in males is mainly associated with the ALDH2*1/1 genotype, while in female patients, the ADH2*1/1 genotype was more highly associated with risk of AD. Overall, it is evident that gender differences associated with genetic risks for AD are present.

Keywords: Alcohol dependence; ADH2; ALDH2; Gender differences; Genetic risk

  • Goodwin DW. Alcoholism and heredity. A review and hypothesis. Arch Gen Psychiatry 1979; 36: 57-61. CrossrefPubMedGoogle Scholar

  • Schuckit MA. Genetics of the risk for alcoholism. Am J Addict 2000; 9: 103-12. CrossrefPubMedGoogle Scholar

  • Dick DM, Foroud T. Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin Exp Res 2003; 27: 868-79. PubMedCrossrefGoogle Scholar

  • Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, Regier DA. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984; 41: 949-58. CrossrefPubMedGoogle Scholar

  • Piazza NJ, Vrbka JL, Yeager RD. Telescoping of alcoholism in women alcoholics. Int J Addict1989; 24: 19-28. PubMedGoogle Scholar

  • Randall CL, Roberts JS, Del Boca, FK, Carroll KM, Connors GJ, Mattson ME. Telescoping of landmark events associated with drinking: a gender comparison. J Stud Alcohol 1999; 60: 252-60. PubMedGoogle Scholar

  • McGue M, Pickens RW, Svikis DS. Sex and age effects on the inheritance of alcohol problems: a twin study. J Abnorm Psychol 1992; 101: 3-17. CrossrefPubMedGoogle Scholar

  • Heath AC, Bucholz KK, Madden PA, Dinwiddie SH, Slutske WS, Bierut LJ, Statham DJ, Dunne MP, Whitfield JB, Martin NG. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 1997; 27: 1381-96. CrossrefGoogle Scholar

  • Prescott CA, Hewitt JK, Truett KR, Heath AC, Neale MC, Eaves LJ. Genetic and environmental influences on lifetime alcohol-related problems in a volunteer sample of older twins. J Stud Alcohol 1994; 55: 184-202. Google Scholar

  • Prescott CA, Kendler KS. Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry 1999; 156: 34-40. Google Scholar

  • Borras E, Coutelle C, Rosell A, Fernandez-Muixi F, Broch M, Crosas B, Hjelmqvist L, Lorenzo A, Gutierrez C, Santos M, Szczepanek M, Heilig M, Quattrocchi P, Farres J, Vidal F, Richart C, Mach T, Bogdal J, Jornvall H, Seitz HK, Couzigou P, Pares X. Genetic polymorphism of alcohol dehydrogenase in Europeans: the ADH2*2 allele decrease the risk for alcoholism and is associated with ADH3*1. Hepatology 2000; 31: 984-9. CrossrefGoogle Scholar

  • Cheng A.T, Gau SF, Chen TH, Chang JC, Chang YT. A 4-year longitudinal study on risk factors for alcoholism. Arch Gen Psychiatry 2004; 61: 184-91. CrossrefPubMedGoogle Scholar

  • Whitfield JB Nightingale BN, Bucholz KK, Madden PA, Heath AC, Martin NG. ADH genotypes and alcohol use dependence in Europeans. Alcohol Clin Exp Res 1998; 22: 1463-9. PubMedCrossrefGoogle Scholar

  • Paik IH, Lee C, Lee SJ, Lee CU, Kim JJ, Jun TY, Han SI, Hahm W. Genetic frequencies of aldehyde dehydrogenase 2 in Korean patients with alcohol dependence. J Korean Neuropsychiatr Asso 1998; 37: Google Scholar

  • Kim ST, Chung HK, Paik YS, Lee KA, Yun KJ, Chang DW, Son BK. The comparison of frequencies of aldehyde dehydrogenase 2(ALDH2) genotypeds and A1 Allele of dopamine D2 receptor(DRD2) gene in Korean male alcohol dependence patients. J Korean Academy Addiction Psychiatry 1999; 3: 129-33. Google Scholar

  • Chung I, Hong J, Lee S, Kim H, Son J. Clinical characteristics and gene polymorphisms of aldehyde dehydrogenase II and arylsulfatase a hospitalized patients with alcohol dependence. J Korean Academy Addiction Psychiatry 2000; 4: 93-101. Google Scholar

  • Chung I, Kim H, Hong J, Chi K, Lee G. An association study between alcohol dependence and candidate genes. J Korean Neuropsychiatry Assoc 2002; 41: 980-90. Google Scholar

  • Chung I, Kim Y, Chi K, Kim H. Association of genetic polymorphisms of aldehyde dehydrogenase II and CYP2E1 and clinical characteristics of patients with alcohol dependence. Korean J Biol Psychiatry 2002; 9: 42-9. Google Scholar

  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Washington, DC, 1994 Google Scholar

  • Lahiri D, Schnabel B. DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA, storage time and temperature on DNA yield and quality. Biochem Genet 1993; 31: 321-8. CrossrefGoogle Scholar

  • Harada S, Zhang S. New strategy for detection of ALDH2 mutant. Alcohol Alcohol Suppl 1993; 1A: 11-3. Google Scholar

  • Groppi A, Begueret J, Iron A. Improved methods for genotype determination of human alcohol dehydrogenase (ADH) at ADH2 and ADH3 loci by using polymerase chain reaction-directed mutagenesis. Clin Chem 1990; 36: 1765-8. PubMedGoogle Scholar

  • Ferguson RA, Goldberg DM. Genetic markers of alcohol abuse. Clin Chim Acta 1997; 257: 199-250. Google Scholar

  • Muramatsu T, Wang ZC, Fang YR, Hu KB, Yan H, Yamada K, Hiquchi S, Harada S, Kono H. Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai. Hum Genet 1995; 96: 151-4. PubMedCrossrefGoogle Scholar

  • Lee KH, Kwak BY, Kim JH, Yoo SK, Yum SK, Jeong HS. Genetic polymorphism of cytochrome P-4502E1 and mitochondrial aldehyde dehydrogenase in a Korean polulation. Alcohol Clin Exp Res 1997; 21: 953-6. Google Scholar

  • Chen WJ, Loh EW, Hsu YP, Chen CC, Yu JM, Cheng AT. Alcohol-metabolizing genes and alcoholism among Taiwanese Han men: independent effect of ADH2, ADH3 and ALDH2. Br J Psychiatry 1996; 68: 762-7. CrossrefGoogle Scholar

  • Maezawa Y, Yamauchi M, Toda G, Suzuki, H, Sakurai S. Alcohol-metabolizing enzyme polymorphisms and alcoholism in Japan. Alcohol Clin Exp Res 1995; 19: 951-4. CrossrefPubMedGoogle Scholar

  • Nakamura K, Iwahashi K, Matsuo Y, Miyatake R, Ichikawa Y, Suwaki H. Characteristics of Japanese alcoholics with the atypical aldehyde dehydrogenase 2*2. I. A comparison of the genotypes of ALDH2, ADH2, ADH3, and cytochrome P-4502E1 between alcoholics and nonalcoholics. Alcohol Clin Exp Res 1996; 20: 52-5. Google Scholar

  • Heath AC, Todorov AA, Nelson EC, Madden PA, Bucholz KK, Martin NG. Gene-environment interaction effects on behavioral variation and risk of complex disorders: the example of alcoholism and other psychiatric disorder. Twin Res 2002; 5: 30-7. PubMedCrossrefGoogle Scholar

  • Heath AC, Whitfield JB, Madden PA, Bucholz KK, Dinwiddie SH, Slutske WS, Bierut LJ, Statham DB, Martin NG. Towards a molecular epidemiology of alcohol dependence: analysing the interplay of genetic and environmental risk factors. Br J Psychiatry Suppl 2001; 40: s33-40. CrossrefGoogle Scholar

  • Brady KT, Grice DE, Dustan L, Randall C. Gender differences in substance use disorders. Am J Psychiatry 1993; 150: 1707-11. PubMedGoogle Scholar

  • Dunne FJ, Galatopoulos C, Schipperheijn JM. Gender differences in psychiatric morbidity among alcohol misusers. Compr. Psychiatry 1993; 34: 95-101. Google Scholar

  • Friedman AS, Kramer S, Kreisher C, Granick S. The relationships of substance abuse to illegal and violent behavior, in a community sample of young adult African American men and women (gender differences). J Subst Abuse 1996; 8: 379-402. CrossrefGoogle Scholar

  • Fischer EH, Goethe JW. Anxiety and alcohol abuse in patients in treatment for depression. Am J Drug Alcohol Abuse, 1998; 24: 453-63. Google Scholar

  • Frezza M, di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med 1990; 322: 95-9.CrossrefGoogle Scholar

About the article

Received: 2012-12-25

Accepted: 2013-03-18

Published Online: 2013-05-10

Citation Information: Addiction Genetics, Volume 1, Pages 12–18, ISSN (Online) 2084-7688, DOI: https://doi.org/10.2478/addge-2013-0001.

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©2012 by Versita. This content is open access.

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