RESEARCH PAPERS: PDF OnlyGenetic variation of the glutamate transporter EAAT2 gene and vulnerability to alcohol dependenceSander, T.a,b; Ostapowicz, A.c; Samochowiec, J.c; Smolka, M.a; Winterer, G.a; Schmidt, L. G.aAuthor Information aDepartment of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany;bDepartment of Neurology, University Hospital Charité, Campus Virchow Clinic, Humboldt University of Berlin, Berlin, Germany;cDepartment of Psychiatry, Pomeranian Medical University, Szczecin, Poland Correspondence to T. Sander, Department of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Eschenallee 3, 14050 Berlin, Germany. Tel: +49 30 8445 8665; Fax: +49 30 8445 8388; E-mail:[email protected] Received 21 December 1999; accepted 10 July 2000 Psychiatric Genetics: September 2000 - Volume 10 - Issue 3 - p 103-107 Buy Abstract Glutamate-mediated excitatory pathways play an important role in the pathogenesis of alcohol dependence. The present association study tested the candidate gene hypothesis that variation of the gene encoding the astroglial glutamate transporterEAAT2confers vulnerability to alcohol dependence. Genotypes of a silent G603A nucleotide exchange in exon 5 of theEAAT2gene were assessed in 565 subjects of German descent, comprising 342 alcohol-dependent subjects and 223 control subjects. Two more homogeneous subgroups of alcoholics were selected: (1) 112 alcoholics with a history of alcohol withdrawal seizure or delirium; and (2) 54 alcoholics with an antisocial personality disorder. The Tridimensional Personality Questionnaire was applied to assess personality dimensions in 106 alcohol-dependent males. The allele frequencies of the G603A polymorphism did not differ significantly between the control subjects and either the entire sample of alcoholics or the alcoholics with severe physiological withdrawal symptoms. Without correction for multiple testing, there was a significant increase of the frequency of the A603 allele in the antisocial alcoholics compared with either the control subjects [X2 = 4.587, 1 degree of freedom (df),P= 0.032] or the alcoholics without ASPD (X2 = 4.968, 1 df,P= 0.026). The personality trait of Harm Avoidance was significantly lower in alcoholics carrying the A603 allele compared with those lacking it (U-test;P= 0.009). These two consistent lines of evidence suggest that genetic variation of theEAAT2gene confers vulnerability to risk-taking behavior in alcoholics. © 2000 Lippincott Williams & Wilkins, Inc.