The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.
The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum.
复制标题
常见多巴胺 D2 受体基因多态性对 D2/3 受体可用性的影响：C957T 作为壳核和腹侧纹状体的关键决定因素。
DOI：
10.1038/tp.2017.45
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发表时间：
2017
影响因子：
6.8
通讯作者：
Zald,DH
中科院分区：
文献类型：
--
作者：
Smith,CT;Dang,LC;Buckholtz,JW;Tetreault,AM;Cowan,RL;Kessler,RM;Zald,DH
多巴胺功能广泛地与多种神经精神疾病有关，这些疾病被认为具有遗传基础。尽管一些正电子发射断层扫描（PET）研究已经调查了多巴胺D2受体基因（DRD 2）中单核苷酸多态性（SNP）对D2/3受体可用性（结合电位，BP ND）的影响，但这些研究往往受到样本量小的限制。此外，D2/3 BP ND（Taq 1A）中最常研究的SNP并不位于DRD 2基因本身，这表明它与其他DRD 2 SNP的连锁可能解释了以前的PET结果。在这里，在迄今为止最大的PET遗传研究（n= 84）中，我们测试了C957 T和-141C Ins/Del SNP（位于DRD 2内）以及Taq 1A对高亲和力D2受体示踪剂18 F-Fallypride的BP ND的影响。在全脑体素分析中，我们发现C957 T T等位基因状态对双侧纹状体BP ND有正线性影响。含有C957 T和一个或两个其他SNP的多位点遗传评分产生了与单独C957 T定性相似的纹状体结果。C957 T T等位基因的数量预测BP ND在解剖定义的壳核和腹侧纹状体（但不是尾状核）的利益，这表明在纹状体的影响的一些区域特异性。相比之下，在皮层区域没有显著的影响。总之，我们的数据支持C957 T在纹状体D2/3受体可用性中的关键作用。这项工作对许多精神疾病有影响，其中多巴胺信号传导和C957 T状态的变化都有牵连，包括精神分裂症和物质使用障碍。
Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BP ND), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BP ND (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n= 84), we tested for effects of the C957T and-141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BP ND of the high-affinity D2 receptor tracer 18 F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BP ND bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BP ND in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.