Martinez D, Gelernter J, Abi-Dargham A, van Dyck C H, Kegeles L, Innis R B, Laruelle M
Division of Functional Brain Mapping, New York State Psychiatry Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Neuropsychopharmacology. 2001 May;24(5):553-60. doi: 10.1016/S0893-133X(00)00216-5.
A 40 base polymorphism of a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). Despite being located in the untranslated region of the gene, this polymorphism has been associated with clinical phenotypes associated with dysregulation of dopamine transmission, such as attention deficit hyperactivity disorder and cocaine-induced paranoia. To examine the neurochemical phenotype associated with this polymorphism, we compared amphetamine-induced dopamine release (measured as displacement of the radiotracer [123I]IBZM) and DAT expression (measured with [123I]beta-CIT) in the striatum with Single Photon Computerized Emission Tomography (SPECT). Our sample included 59 subjects, 31 healthy controls and 29 patients with schizophrenia. No significant association was found between VNTR polymorphism and amphetamine-induced dopamine release or DAT density in the total sample, nor when each diagnostic group was considered separately. Thus, we did not replicate the findings of two previous studies, which had suggested that the 9 repeat allele was associated with either an increased or decreased DAT expression, albeit in different patient populations.
在编码多巴胺转运体（DAT）的基因（SLC6A3）的3'非翻译区，已发现一种可变数目串联重复序列（VNTR）的40个碱基多态性。尽管该多态性位于基因的非翻译区，但它已与多巴胺传递失调相关的临床表型有关，如注意力缺陷多动障碍和可卡因诱发的偏执狂。为了研究与这种多态性相关的神经化学表型，我们使用单光子计算机发射断层扫描（SPECT）比较了纹状体中苯丙胺诱导的多巴胺释放（以放射性示踪剂[123I]IBZM的位移来衡量）和DAT表达（用[123I]β-CIT测量）。我们的样本包括59名受试者，31名健康对照者和29名精神分裂症患者。在整个样本中，未发现VNTR多态性与苯丙胺诱导的多巴胺释放或DAT密度之间存在显著关联，分别考虑每个诊断组时也未发现。因此，我们没有重复之前两项研究的结果，这两项研究表明9重复等位基因与DAT表达的增加或减少有关，尽管是在不同的患者群体中。
