Functional effects of dopamine transporter gene genotypes on in vivo dopamine transporter functioning: a meta-analysis
Functional effects of dopamine transporter gene genotypes on in vivo dopamine transporter functioning: a meta-analysis
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DOI：
10.1038/mp.2013.126
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发表时间：
2014-08-01
影响因子：
11
通讯作者：
Biederman, J.
中科院分区：
文献类型：
--
作者：
Faraone, S. V.;Spencer, T. J.;Biederman, J.
许多精神病遗传学研究集中在位于多巴胺主动转运蛋白（DAT）基因（SLC 6A 3）的30个非翻译区（30 UTR）的40个碱基对可变数目串联重复序列（VNTR）多态性。这种变体产生两种常见的等位基因，分别为9个和10个重复序列（9 R和10 R）。将该变体与人体内DAT活性相关联的研究结果喜忧参半。我们检索了使用正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）来评估这种关联的研究。随机效应荟萃分析评估了30 UTR变异与DAT活性的关联。我们还评估了研究之间的异质性和发表偏见的证据。我们发现了12项研究，包括511名受试者，125名来自PET研究，386名来自SPECT研究。PET研究提供了非常重要的证据，证明9 R等位基因与成人DAT活性增加相关。SPECT研究具有高度异质性。作为一个群体，他们认为30 UTR多态性和DAT活性之间没有关联。当分析仅限于最常用的配体[123 I] b-CIT时，根据患病状态分层显著降低了异质性，并揭示了健康受试者中9 R等位基因与DAT活性增加的显著相关性。在人类中，SLC 6A 3 30 UTR多态性的9 R等位基因调节纹状体脑区的多巴胺活性，与神经精神疾病的存在无关。研究方法的差异导致了个体研究结果的异质性。
Much psychiatric genetic research has focused on a 40-base pair variable number of tandem repeats (VNTR) polymorphism located in the 30-untranslated region (30UTR) of the dopamine active transporter (DAT) gene (SLC6A3). This variant produces two common alleles with 9- and 10-repeats (9R and 10R). Studies associating this variant with in vivo DAT activity in humans have had mixed results. We searched for studies using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) to evaluate this association. Random effects meta-analyses assessed the association of the 30UTR variant with DAT activity. We also evaluated heterogeneity among studies and evidence for publication bias. We found twelve studies comprising 511 subjects, 125 from PET studies and 386 from SPECT studies. The PET studies provided highly significant evidence that the 9R allele was associated with increased DAT activity in human adults. The SPECT studies were highly heterogeneous. As a group, they suggested no association between the 30UTR polymorphism and DAT activity. When the analysis was limited to the most commonly used ligand, [123I] b-CIT, stratification by affection status dramatically reduced heterogeneity and revealed a significant association of the 9R allele with increased DAT activity for healthy subjects. In humans, the 9R allele of the 30UTR polymorphism of SLC6A3 regulates dopamine activity in the striatal brain regions independent of the presence of neuropsychiatric illness. Differences in study methodology account for the heterogeneous results across individual studies.