患有注意力缺陷多动障碍（ADHD）的成年人对哌甲酯的反应与溶质载体家族6成员3（SLC6A3，即多巴胺转运体1，DAT1）的一个基因多态性有关。

Response to methylphenidate in adults with ADHD is associated with a polymorphism in SLC6A3 (DAT1).

作者信息

Kooij J Sandra, Boonstra A Marije, Vermeulen Sita H, Heister Angelien G, Burger Huibert, Buitelaar Jan K, Franke Barbara

机构信息

PsyQ, Psycho-Medical Programs, The Hague, The Netherlands.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2008 Mar 5;147B(2):201-8. doi: 10.1002/ajmg.b.30586.

DOI:10.1002/ajmg.b.30586

PMID:17955457

Abstract

In this pharmacogenetic study in adults with ADHD (n = 42), a stratified analysis was performed of the association between response to methylphenidate (MPH), assessed under double-blind conditions, and polymorphisms in the genes encoding the dopamine transporter, SLC6A3 (DAT1), the norepinephrine transporter, SLC6A2 (NET), and the dopamine receptor D4, DRD4. The VNTR polymorphism in the 3' untranslated region of SLC6A3 was significantly associated with an increased likelihood of a response to MPH treatment (OR 3.8; 95% CI 1.0-15.2, and OR 5.4; 95% CI 1.4-21.9, depending on the definition of response) in carriers of a single 10-repeat allele compared to patients with the 10/10 genotype. The polymorphisms in DRD4 and the SLC6A2 were not associated with treatment response. This study supports a role of the SLC6A3 genotype in determining the response to MPH in the treatment of adults with ADHD.

摘要

在这项针对成人注意力缺陷多动障碍（ADHD，n = 42）的药物遗传学研究中，对在双盲条件下评估的哌甲酯（MPH）反应与编码多巴胺转运体SLC6A3（DAT1）、去甲肾上腺素转运体SLC6A2（NET）和多巴胺受体D4（DRD4）的基因多态性之间的关联进行了分层分析。与具有10/10基因型的患者相比，在携带单个10重复等位基因的个体中，SLC6A3 3'非翻译区的可变数目串联重复多态性（VNTR）与MPH治疗反应增加的可能性显著相关（根据反应定义，OR分别为3.8；95%CI 1.0 - 15.2和OR 5.4；95%CI 1.4 - 21.9）。DRD4和SLC6A2的多态性与治疗反应无关。本研究支持SLC6A3基因型在成人ADHD治疗中对MPH反应的决定作用。