多巴胺β-羟化酶基因与注意缺陷多动障碍及其候选内表型的关联研究

项目名称： 多巴胺β-羟化酶基因与注意缺陷多动障碍及其候选内表型的关联研究

项目编号： No.81201059

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 吉宁

作者单位： 北京大学

项目金额： 23万元

中文摘要： 注意缺陷多动障碍是异质性很强的复杂遗传性疾病。多巴胺β-羟化酶(DβH)催化多巴胺(DA)转化为去甲肾上腺素(NE)，对维持与ADHD及其认知功能密切相关脑区(如前额叶)的 DA/NE平衡具有重要作用。本研究组前期关注于候选基因研究- - 发现多巴胺β羟化酶基因(DBH)可能与ADHD及其认知功能(反应时、干扰抑制能力)存在关联。血浆DβH活性主要受控于DBH基因，在个体间差异悬殊，但对同一个体则相对稳定，是研究ADHD较好的内表型之一。本研究拟纳入1000例患儿(含500-800核心家系)和500例正常对照，获得表型、认知功能资料，检测DBH基因型、血浆DβH活性，旨在探讨DBH基因与血浆DβH活性的关系(特别是在家系资料中)，探讨ADHD及其亚型的血浆DβH活性特点，以及ADHD和正常对照中认知功能与血浆DβH活性的关系。本项目预期发现ADHD新的生物标记，进而探讨ADHD潜在的病理机制。

中文关键词： 注意缺陷多动障碍；多巴胺β-羟化酶；单核苷酸多态性；关联；内表型

英文摘要： Attention-deficit/hyperactivity disorder (ADHD) is a common, etiologically heterogeneous complex disorder with high heritability. Synthesis of norepinephrine(NE) from dopamine(DA) is catalyzed by the enzyme dopamine β-hydroxylase(DβH), which is essential for the balance of DA/NE in cortical areas associated with ADHD and its cognitive functions (e.g. prefrontal cortex). Previous study of our team suggested that dopamine β-hydroxylase(DBH) gene is associated with ADHD and its endophenotypes (reaction time and interference control). Numerous polymorphisms in the DBH gene have been found to exert their direct influence on the plasma DβH activity (pDβH) independently, and pDβH varies between individuals but stable within subjects, which suggests pDβH as a good endophenotype of ADHD. In the present study, 1000 ADHD children (including 500-800 trios) and 500 sex- and age-matched unaffected controls will be enrolled with phenotype data, cognitive functions, genotypes of DBH gene and pDβH activity. The aim of this work is to assess the association between DBH gene and pDβH activity (especially in trios), the characteristics of pDβH activity in ADHD and its subtypes, and the association between pDβH activity and cognitive functions in ADHD and controls. We anticipate to find new biomarker and explore the etiology and pat

英文关键词： Attention deficit hyperactivity disorder；dopamine β-hydroxylase；single nucleotide polymorphism；association；endophenotype