Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Synapse. 2011 Oct;65(10):998-1005. doi: 10.1002/syn.20927. Epub 2011 Mar 28.
The human dopamine transporter (DAT) gene (SLC6A3) contains a 40-bp variable number of tandem repeats (VNTR) polymorphism. A number of studies have investigated the association of this VNTR with striatal DAT availability in humans using single photon emission computed tomography (SPECT). However, the results are not consistent. Therefore, we carried out a meta-analysis of the association between the SLC6A3 VNTR and striatal DAT binding measured in human SPECT studies. The meta-analysis of five samples of healthy individuals failed to find a significant difference in DAT availability between SLC6A3 9-repeat carriers and 10-repeat homozygotes (P = 0.22) although the 9R carriers had nominally higher striatal DAT levels (g = 0.66). The results remained nonsignificant after the inclusion of patient samples, namely schizophrenia, attention deficit hyperactivity disorder, and Parkinson's disease (four samples; all P > 0.18). To conclude, this meta-analysis provides no evidence to support the hypothesis that the SLC6A3 VNTR is significantly associated with interindividual differences in DAT availability in the human striatum. Further work is needed to clarify the molecular mechanisms by which this polymorphism may affect cognition and psychiatric disorders, if not through altered expression as measured by molecular imaging.
人类多巴胺转运蛋白（DAT）基因（SLC6A3）含有一个 40 个碱基对的可变串联重复（VNTR）多态性。许多研究已经使用单光子发射计算机断层扫描（SPECT）研究了这种 VNTR 与人类纹状体 DAT 可用性之间的关联。然而，结果并不一致。因此，我们对 SPECT 研究中 SLC6A3 VNTR 与纹状体 DAT 结合的关联进行了荟萃分析。对五个健康个体样本的荟萃分析未能发现 SLC6A3 9 重复携带者和 10 重复纯合子之间 DAT 可用性存在显著差异（P = 0.22），尽管 9R 携带者的纹状体 DAT 水平名义上更高（g = 0.66）。在纳入患者样本（包括精神分裂症、注意缺陷多动障碍和帕金森病的四个样本；所有 P > 0.18）后，结果仍然没有统计学意义。总之，这项荟萃分析没有提供证据支持 SLC6A3 VNTR 与人类纹状体中 DAT 可用性的个体差异显著相关的假设。如果不是通过分子成像测量的表达改变，那么需要进一步的工作来阐明这种多态性如何影响认知和精神疾病的分子机制。
