Walitza Susanne, Scherag André, Renner Tobias J, Hinney Anke, Remschmidt Helmut, Herpertz-Dahlmann Beate, Schulz Eberhard, Schafer Helmut, Lange Klaus W, Wewetzer Christoph, Gerlach Manfred
Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany.
J Neural Transm (Vienna). 2008 Jul;115(7):1071-8. doi: 10.1007/s00702-008-0051-6. Epub 2008 Apr 30.
The dopaminergic system has been shown to be involved in the aetiology of obsessive-compulsive disorder (OCD). Family studies suggest a higher genetic loading in patients with early onset OCD. Our investigation is the first family-based association study concerning polymorphisms in genes of the dopaminergic system in early onset OCD. We studied polymorphisms within the dopamine-4 receptor gene (DRD4), the dopamine transporter gene (DAT1) and the catecholamine-O-methyltransferase gene (COMT). Associations of alleles of DRD4 and COMT with OCD have previously been reported in adults, while a trend towards an association was found for DAT1 alleles. In our study we observed transmission disequilibrium for the 48-bp repeat polymorphism of the DRD4 gene using the ETDT (P=0.047) in 69 trios comprising patients with early onset OCD and both of their parents. Post hoc TDT analysis of the DRD4 showed reduced transmission of the 4-repeat allele and a slightly increased transmission rate for the 7- and the 2-repeat allele. No evidence of transmission disequilibrium was detected for alleles of the DAT1 and COMT polymorphisms. These polymorphisms do not appear to play a major role in the genetic predisposition to early onset OCD in our study group.
多巴胺能系统已被证明与强迫症（OCD）的病因有关。家族研究表明，早发性强迫症患者的遗传负荷更高。我们的研究是第一项基于家族的关于早发性强迫症患者多巴胺能系统基因多态性的关联研究。我们研究了多巴胺 - 4受体基因（DRD4）、多巴胺转运体基因（DAT1）和儿茶酚 - O - 甲基转移酶基因（COMT）内的多态性。此前已有报道称，DRD4和COMT的等位基因与成人强迫症有关，而DAT1等位基因也存在关联趋势。在我们的研究中，我们使用ETDT对69个三联体（包括早发性强迫症患者及其父母）进行了DRD4基因48bp重复多态性的传递不平衡检验（P = 0.047）。DRD4的事后TDT分析显示，4重复等位基因的传递减少，而7重复和2重复等位基因的传递率略有增加。未检测到DAT1和COMT多态性等位基因存在传递不平衡的证据。在我们的研究组中，这些多态性似乎在早发性强迫症的遗传易感性中不起主要作用。
