Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence

Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence

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J Psychiatry Neurosci 2007;32(3):185-92

San-Yuan Huang, MD; Wei-Wen Lin, MD; Fang-Jung Wan, MD; Ai-Ju Chang, MS; Huei-Chen Ko, PhD; Tso-Jen Wang, MD; Pei-Lin Wu, BS; Ru-Band Lu, MD

Huang, Lin, Wan, Chang, Lu — Department of Psychiatry, Tri-Service General Hospital; Wang — Graduate Institute of Medical Sciences, National Defense Medical Center, National Defense Medical Center, Taipei; Chang — Program of Clinical Psychology, Department of Psychology, National Taiwan University, Taipei; Ko, Lu — Institute of Behavioral Medicine; Lu — Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan; Wang — Department of Health, Nantau Psychiatric Center, Nantau, Taiwan, ROC.

Abstract

Objective: Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of biogenic amines. Therefore, the present study investigates whether the association between the dopamine D2 receptor (DRD2) gene and alcoholism is affected by different polymorphisms of the MAO type A (MAOA) gene.
Methods: A total of 427 Han Chinese men in Taiwan (201 control subjects and 226 with alcoholism) were recruited for the study. Of the subjects with alcoholism, 108 had pure alcohol dependence (ALC) and 118 had both alcohol dependence and anxiety, depression or both (ANX/DEP ALC). All subjects were assessed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime. Alcohol dependence, anxiety and major depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria.
Conclusion: The genetic variant of the DRD2 gene was only associated with the ANX/DEP ALC phenotype, and the genetic variant of the MAOA gene was associated with pure ALC. Subjects carrying the MAOA 3-repeat allele and genotype A1/A1 of the DRD2 were 3.48 times (95% confidence interval = 1.47-8.25) more likely to be ANX/DEP ALC than the subjects carrying the MAOA 3-repeat allele and DRD2 A2/A2 genotype. The MAOA gene may modify the association between the DRD2 gene and ANX/DEP ALC phenotype.

Résumé

Objectif : La faible activité de la monoamine oxydase (MAO) et la dopamine neurotransmettrice sont deux facteurs importants de l’apparition de l’accoutumance à l’alcool. La MAO est une enzyme importante associée au métabolisme des amines biogéniques. La présente étude vise donc à déterminer si des polymorphismes différents du gène de la MAO type A (MAOA) ont un effet sur le lien entre le gène du récepteur D2 de la dopamine (RDD2) et l’alcoolisme.
Méthodes : On a recruté au total, pour l’étude, 427 hommes chinois Han à Taiwan (201 sujets témoins et 226 atteints d’alcoolisme). Parmi les sujets alcooliques, 108 avaient une dépendance pure à l’alcool (ALC) et 118 avaient à la fois une dépendance à l’alcool et de l’anxiété, de la dépression, ou les deux (ANX/DEP ALC). On a évalué tous les sujets au moyen de la version chinoise du Guide modifié pour le diagnostic des troubles affectifs et de la schizophrénie. On a diagnostiqué la dépendance à l’alcool, l’anxiété et les troubles dépressifs majeurs selon les critères du Manuel diagnostique et statistique des troubles mentaux, quatrième édition.
Conclusion : On a établi un lien entre la variante génétique du gène du RDD2 et le phénotype ANX/DEP ALC seulement et entre la variante génétique du gène MAOA et la dépendance pure à l’alcool. Les sujets porteurs de l’allèle triple MAOA 3 et du génotype A1/A1 du gène du RDD2 étaient 3,48 fois (intervalle de confiance à 95 % = 1,47–8,25) plus susceptibles d’avoir le trouble ANX/DEP ALC que les sujets porteurs de l’allèle triple MAOA et du génotype A2/A2 du RDD2. Le gène MAOA a peu modifié le lien entre le gène du RDD2 et le phénotype ANX/DEP ALC.


Medical subject headings: alcoholism, anxiety, depression, dopamine D2receptor, monoamine oxidase.

Competing interests: None declared.

Acknowledgements: This study was supported in part by National Science Council Grants NSC 92-2314-B-006-151, NSC93-2314-B-006-108, NSC94-2314-B-006-116, NSC94-2314-B-016-016 and NSC95-2314-B-016-019; the Department of Health Grants DOH 88-TD-1107 and DOH94-TD-D-113-040; Tri-Service General Hospital Grant TSGH-C94-76, and by National Cheng Kung University Project of Promoting Academic Excellence and Developing World Class Research Centers, Taiwan, Republic of China. Thanks to Mr. Cheng-Chang Huang, A-Lan Tang and Fu-Kuei Chang for their assistance in preparing this manuscript.

Contributors: Drs. Huang, Lin, Ko, and Lu, Ms. Chang and Ms. Wu designed the study. Drs. Huang, Wan, Wang and Lu, Ms. Chang and Ms. Wu aquired the data, which Drs. Huang, Lin, and Lu, and Ms. Wu analyzed. Drs. Huang and Lu wrote the article, and all authors revised it. All authors gave final approval for the article to be published.

Submitted June 30, 2006; Revised Sept. 22, 2006; Accepted Oct. 4, 2006

Correspondence to: Dr. Ru-Band Lu, Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, No. 138, Sheng-Li Road, 70428, Tainan, Taiwan, ROC; fax 886-6-302-8012; rblu@mail.ncku.edu.tw