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Interaction between gene variants of the serotonin transporter promoter region (5‐HTTLPR) and catechol O ‐methyltransferase (COMT) in borderline personality disorder
Author(s) -
Tadić André,
Victor Anja,
Başkaya Ömür,
von Cube Robert,
Hoch Julia,
Kouti Ioanna,
Anicker Nina J.,
Höppner Wolfgang,
Lieb Klaus,
Dahmen Norbert
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30843
Subject(s) - catechol o methyl transferase , serotonin transporter , borderline personality disorder , 5 httlpr , genotype , psychology , allele , snp , single nucleotide polymorphism , medicine , endocrinology , genetics , clinical psychology , gene , biology
Borderline personality disorder (BPD) is characterized by a heterogeneous symptomatology with instability in impulse control, interpersonal relationships and self‐image. BPD patients display repeated self‐injury, chronic suicidal tendencies and emotional dysregulation, mainly dysregulation of negative affect. In its etiology, genetic and environmental factors have been suggested. Recently, an investigation in male healthy volunteers found gene–gene effects of the catechol‐ O ‐methyl‐transferase (COMT) low‐activity (Met 158 ) and the low‐expression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporter‐linked promoter region (5‐HTTLPR) on the central processing of aversive stimuli. The purpose of the present study was to test for association between BPD and the COMT Val 158 Met single nucleotide polymorphism (SNP), the 5‐HTTLPR S/L variant and the interaction of these two gene variants. One hundred sixty one well‐defined Caucasian BPD patients and 156 healthy controls were recruited from central Germany. In BPD patients, the genotype COMT Met 158 Met was over‐represented compared to healthy controls ( P = 0.0085; adjusted P = 0.034). We observed no differences in 5‐HTTLPR genotypes between BPD and controls ( P = 0.286). Additionally, the COMT Met 158 Met genotype was significantly over‐represented in BPD patients carrying at least one 5‐HTTLPR S allele ( P = 0.0007; adjusted P = 0.028). Logistic regression analysis confirmed an interaction of the COMT Met 158 and the 5‐HTTLPR S allele ( P = 0.001). These data suggest an involvement of altered dopaminergic and/or noradrenergic neurotransmission as well as an interactive effect of COMT and 5‐HTTLPR gene variants in the etiology of BPD, and underline the usefulness of analyses of gene–gene effects in diseases of complex inheritance with multiple genes involved. © 2008 Wiley‐Liss, Inc.