Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 144, Taiwan, ROC.
Eur Arch Psychiatry Clin Neurosci. 2018 Apr;268(3):249-260. doi: 10.1007/s00406-016-0754-x. Epub 2016 Dec 27.
The dopamine receptor D3 (DRD3) gene, one of the candidate genes for amphetamine dependence (AD), is involved in the mesolimbic dopaminergic system, implicated as the underlying mechanism of addiction. Our case-control study aimed to investigate whether the DRD3 gene is associated with the susceptibility to AD and specific personality traits in AD patients. A total of 1060 unrelated Han Chinese subjects (559 AD patients and 501 controls) were screened using the same assessment tool and genotyped for eight DRD3 polymorphisms. All patients met the DSM-IV-TR criteria for AD, and personality traits of 539 were assessed using a Tridimensional Personality Questionnaire. Furthermore, AD individuals were divided into four clinical subgroups based on gender and psychosis status, to reduce the clinical heterogeneity. We found that the ATA haplotype combination for SNPs rs324029, rs6280, and rs9825563, respectively, was significantly associated with total AD patients (p = 0.0003 after 10,000 permutations). Similar results were observed in the both male and non-psychosis subgroup but not in other subgroups. In addition, DRD3 rs9825563 may influence onset age of drug use, partially mediated by novelty seeking in the non-psychosis AD group. In conclusion, DRD3 is a potential genetic factor in the susceptibility to AD and is associated with onset age of drug use through interaction with novelty seeking in a specific patient group in the Han Chinese population.
多巴胺受体 D3 (DRD3) 基因是安非他命依赖（AD）的候选基因之一，参与中脑边缘多巴胺能系统，被认为是成瘾的潜在机制。我们的病例对照研究旨在探讨 DRD3 基因是否与 AD 的易感性以及 AD 患者的特定人格特征有关。我们使用相同的评估工具筛选了 1060 名无关汉族个体（559 名 AD 患者和 501 名对照），并对 8 个 DRD3 多态性进行了基因分型。所有患者均符合 DSM-IV-TR 中 AD 的诊断标准，对 539 名患者的人格特征使用三维人格问卷进行了评估。此外，根据性别和精神病状态将 AD 个体分为四个临床亚组，以减少临床异质性。我们发现，分别位于 rs324029、rs6280 和 rs9825563 三个 SNP 的 ATA 单倍型组合与总 AD 患者显著相关（经过 10000 次置换检验后，p=0.0003）。在男性和非精神病亚组中也观察到了相似的结果，但在其他亚组中则没有。此外，DRD3 rs9825563 可能通过影响非精神病 AD 组中的寻求新奇，影响药物使用的发病年龄。总之，DRD3 是 AD 易感性的潜在遗传因素，与汉族人群中特定患者群体中寻求新奇的相互作用与药物使用的发病年龄有关。
