多巴胺β羟化酶基因与伴破坏性行为障碍的注意缺陷多动障碍的关联分析  

Association between dopamine β hydroxylase gene and attention deficit hyperactivity disorder complicated with disruptive behavior disorder

作　　者：张浩波[1] 王玉凤[1] 李君[1] 汪冰[1] 杨莉[1] 

机构地区：[1]北京大学精神卫生研究所儿童室,100083

出　　处：《中华儿科杂志》2005年第1期26-30,共5页Chinese Journal of Pediatrics

基　　金：科技部攀登计划基金资助项目 (95 -专 -0 9);卫生部临床学科重点项目 (2 0 0 4)

摘　　要：目的　分析去甲肾上腺素的合成限速酶———多巴胺 β羟化酶基因 (DBH)在伴或不伴破坏性行为障碍 (DBD)的注意缺陷多动障碍 (ADHD)核心家系中的传递情况 ,探讨伴或不伴DBD的ADHD与DBH基因之间的关系。方法　以DSM IV诊断标准为依据 ,选择 2 92例ADHD核心家系作为研究对象 ,选取DBH 5′侧翼序列的 - 10 2 1C→T多态为遗传标记 ,通过PCR扩增 ,酶切和电泳确定DBH- 10 2 1C→T多态的基因型。采用传递不平衡检验 (TDT)分析DBH - 10 2 1C→T多态在伴或不伴DBD的ADHD核心家系中的传递情况。结果　DBH - 10 2 1C→T多态在伴或不伴DBD的ADHD中均存在传递不平衡 ,前者优先传递T等位基因 (P <0 0 5 ) ;后者优先传递C等位基因 (P <0 0 5 )。考虑到ADHD亚型的影响 ,DBH - 10 2 1C→T多态仅在ADHD C伴DBD组中存在传递不平衡 ,优先传递T等位基因 (P <0 0 5 )。结论　伴或不伴DBD的ADHD与DBH - 10 2 1C→T多态均存在关联 ,但优先传递的等位基因不同 ,前者优先传递的是低活性的T等位基因 ,而后者优先传递的是高活性的C等位基因 ,提示伴与不伴DBD的ADHD在遗传机制上存在差异。结合ADHD亚型分析 ,仅ADHD C伴DBD与DBH - 10 2 1C→T多态存在关联 ,提示在ADHD 3种亚型中二者的关系可能较为密切。Objective Attention deficit hyperactivity disorder (ADHD), a common behavior disorder of childhood, is a highly heterogeneous disease frequently accompanied by various mental disorders, including disruptive behavior disorder (DBD) Studies show that children suffering from ADHD with DBD are at higher risk of antisocial personality, substance abuse, and social adaptations disorder at their adulthood The dopamine β hydroxylase (DβH) is the key enzyme to ADHD since it catalyzes the conversion of dopamine to norepinephrine, and dysfunction there of is believed to be one of the causes of the disorder To explore the association between DBH gene and ADHD complicated with or without DBD, the authors analyzed the transmission of a novel polymorphism DBH -1021C→T, which is found associated with plasma DβH activity, in ADHD nuclear families using transmission disequilibrium test (TDT) Methods Consensus diagnoses were based on the DSM IV The samples included those from 292 Chinese Han nuclear families with ADHD probands Genotypes of DBH -1021C→T polymorphism were determined by PCR amplification, endonuclease digesting and electrophoresis The transmission of DBH -1021C→T polymorphism in ADHD nuclear families with or without DBD was analyzed by TDT Results The results showed that there was transmission disequilibrium between DBH-1021C→T polymorphism and ADHD with or without DBD In ADHD comorbid with DBD, T allele was preferentially transmitted ( P <0 05); and in ADHD without DBD, so was the C allele ( P <0 05) Among the three subtypes of ADHD, only ADHD C subtype with DBD had an increased transmission of T allele ( P <0 05) Conclusion There is an association between DBH gene and ADHD comorbid with or without DBD, but the preferential transmission alleles are different The low activity T allele is increased to transmit in ADHD with DBD, while the high activity C allele is preferentially transmitted in ADHD without DBD The results support the proposition that the genetic mechani

关 键 词：ADHD 等位基因 多巴胺Β羟化酶 核心家系 注意缺陷多动障碍 亚型 多态 破坏性行为 优先 结论 

分 类 号：R749.94[医药卫生—神经病学与精神病学] R748[医药卫生—临床医学]