Tadić André, Victor Anja, Başkaya Omür, von Cube Robert, Hoch Julia, Kouti Ioanna, Anicker Nina J, Höppner Wolfgang, Lieb Klaus, Dahmen Norbert
Department of Psychiatry and Psychotherapy, University of Mainz, Germany.
Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):487-95. doi: 10.1002/ajmg.b.30843.
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.
边缘型人格障碍（BPD）的特征是症状多样，在冲动控制、人际关系和自我形象方面存在不稳定。BPD患者表现出反复的自我伤害、慢性自杀倾向和情绪失调，主要是负面情绪的失调。在其病因方面，已提出遗传和环境因素。最近，一项针对男性健康志愿者的调查发现，儿茶酚-O-甲基转移酶（COMT）低活性（Met(158)）基因与血清素转运体相关启动子区域（5-HTTLPR）缺失/插入（分别为短/长或S/L）多态性的低表达等位基因在厌恶刺激的中枢处理上存在基因-基因效应。本研究的目的是测试BPD与COMT Val(158)Met单核苷酸多态性（SNP）、5-HTTLPR S/L变体以及这两种基因变体之间的相互作用。从德国中部招募了161名明确诊断的白种人BPD患者和156名健康对照。与健康对照相比，BPD患者中COMT Met(158)Met基因型的比例过高（P = 0.0085；校正后P = 0.034）。我们观察到BPD患者和对照之间5-HTTLPR基因型没有差异（P = 0.286）。此外，在携带至少一个5-HTTLPR S等位基因的BPD患者中，COMT Met(158)Met基因型的比例显著过高（P = 0.0007；校正后P = 0.
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