title: Interaction between gene variants of the serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT) in borderline personality disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Mainz, Germany. tadic@uni-mainz.de
authors.forename: André
authors.initials: A
authors.lastname: Tadić
authors.forename: Anja
authors.initials: A
authors.lastname: Victor
authors.forename: Omür
authors.initials: O
authors.lastname: Başkaya
authors.forename: Robert
authors.initials: R
authors.lastname: von Cube
authors.forename: Julia
authors.initials: J
authors.lastname: Hoch
authors.forename: Ioanna
authors.initials: I
authors.lastname: Kouti
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Anicker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höppner
authors.forename: Klaus
authors.initials: K
authors.lastname: Lieb
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen