多巴胺D4受体基因多态与共患破坏性行为障碍的注意缺陷多动障碍的关联分析

Association analysis of dopamine D4 receptor gene polymorphism and attention deficit hyperactivity disorder with/without disruptive behavior disorder

目的:探讨共患和不共患破坏性行为障碍(DBD)的儿童注意缺陷多动障碍(ADHD)与多巴胺D4受体(DRD4)基因上游调控区-521C/T多态之间的关联。方法:对401例符合美国《精神障碍诊断与统计手册(第4版)》(DSMⅣ-)诊断标准的中国汉族ADHD患儿(包含284个完整核心家系)进行-521C/T多态的基因型检测,采用卡方检验和传递不平衡检验(TDT)分别对共患和不共患DBD的ADHD进行统计分析。结果:(1)ADHD共患DBD组(n=143)T等位基因(χ2=6.778,P=0.009,OR=1.485)和TT基因型(χ2=6.292,P=0.012,OR=1.729)的频率明显高于不共患DBD组(n=258);(2)在共患DBD的ADHD核心家系(n=100)中,T等位基因优先传递(χ2=3.868,P=0.049);在不共患DBD的ADHD家系(n=184)中,未观察到任何等位基因的传递不平衡现象(χ2=0.223,P=0.637)。结论:DRD4基因-521C/T多态与共患DBD的ADHD存在关联。ADHD共患DBD与否可能存在遗传学上的差异。

Objective ： To examine the role of dopamine D4 receptor gene （DRD4） in attention deficit hyperactivity disorder （ADHD） with/without disruptive behavior disorder （DBD） by focusing on a -521C/T SNP within the promoter region of this gene. Methods： A total of 401 DSM-Ⅳ ADHD children （ including 284 trios） of Chinese Han descent were genotyped. Chi-square test and the transmission disequilibrium test （TDT） were used to test for associations in ADHD with and without DBD respectively. Results： In the comparison of ADHD with （n = 143） and without （n = 258） DBD, the -521T allele （χ^2= 6.778, P= 0.009, OR= 1.485） and the TT genotype （χ^2= 6.292,P= 0.012,OR = 1.729） showed higher frequency in children with ADHD and DBD simultaneously. For family based analysis, T allele of the -521C/T polymorphism was preferentially transmitted to ADHD children with comorbid DBD （n = 100, χ^2=3. 868 ,P = 0. 049 ）, whereas no significant distortion was found in the transmission of the tested variant for ADHD without DBD （n = 184, χ^2=0.223 ,P = 0.637）. Conclusion： Our find- ings suggest that the -521C/T SNP of DRD4 may contribute to the predisposition to ADHD with comorbid DBD. This study supports for the hypothesis that ADHD with comorbid DBD may be influenced by greater genetic effect compared to ADHD alone.