CYP2D6基因多态与托莫西汀治疗儿童注意缺陷多动障碍反应的关联研究  

Association of better atomoxetine response with polymorphisms of CYP2D6 gene in the treatment of attention-deficit/hyperactivity disorder

作　　者：方妍彤[1] 陈敏[2,3] 吉宁 曹庆久[2,3] 苏怡[2,3] 杨莉[2,3] 王玉凤[2,3] 

机构地区：[1]杭州师范大学附属医院,杭州310015 [2]北京大学第六医院 [3]北京大学精神卫生研究所卫生部精神卫生学重点实验室(北京大学),北京100191

出　　处：《中国心理卫生杂志》2015年第6期401-405,共5页Chinese Mental Health Journal

基　　金：国家自然科学基金81471381;国家自然科学基金81201059;国家重点基础研究发展计划项目(973)2014CB846100

摘　　要：目的：研究细胞色素酶CYP2D6基因多态与托莫西汀治疗注意缺陷多动障碍（ADHD）临床疗效的关联。方法：选取111例符合美国精神障碍诊断统计手册第4版（DSM-IV）诊断标准的汉族ADHD患儿,经8-12周的托莫西汀开放剂量滴定,至1.2-1.4 mg/kg.d的治疗剂量维持治疗至少4周。在基线和获得最佳剂量4周后使用ADHD评定量表（ADHD-RS）评估行为变化,以ADHD-RS减分作为主要疗效评估指标,以治疗后ADHD-RS各条目评分≤1为缓解标准。选择CYP2D6基因的3个SNPs（rs1080985,rs1065852,rs16947）检测多态性,使用荧光定量PCR仪进行聚合酶链反应（PCR）并判读基因型。结果：本研究未能发现单个多态性与托莫西汀治疗反应的关联（P〉0.05）。单体型分析发现GAC单体型与缓解状态的关联有统计学意义[缓解vs.未缓解单体型频数（率）：5/56（8.9%）vs.3/164（1.8%）,P〈0.05],多重检验校正后仍存在显著性趋势（P=0.082）;与有效状态的关联分析也发现GAC单体型与有效存在关联趋势（P=0.078）,8例携带者全部为治疗有效的患者,无效的患者中无此单体型。结论：本研究提示CYP2D6基因多态性可能与托莫西汀治疗ADHD的临床症状改善存在关联,但还需要在大样本中进一步验证。Objective：To explore the association between CYP2D6 gene polymorphism of cytochrome and clinical response to atomoxetinein children with attention-deficit/hyperactivity disorder.Methods：Totally 111 Han Chinese boys meeting criteria for ADHD in the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edi-tion （DSM-IV）were recruited.Atomoxetine treatment was given in titrated doses in order to achieve optimal re-sponse.Behavior changes were measured with the ADHD Rating Scale （ADHD-RS）at baseline and after optimal doses were reached.The decrease of ADHD-RS scores were primary measures of the treatment effect,the scores of the items in the ADHD-RS was less than or equal to 1 for the remission criteria.The three SNPs of CYP2D6 genes（rs1080985,rs1065852,rs16947）were genotyped by polymerase chain reaction （PCR）.Results：There was no asso-ciation between single polymorphisms andatomoxetine after adjusting for baseline rating scores （P 〉0.05）.In con-trast,haplotype analysis revealed that some patients with GAC haplotype achieved significant remission [remission vs.non-remission haplotype frequency （rate）：5 /56 （8.9%）vs.3 /164（1.8%）,P 〈0.05 ].After multiple testing correction still existed significant trend（P =0.082）and also found correlation trends after correlation analysis be-tween GAC haplotype and clinical response to atomoxetine （P =0.078）,8 patients with GAC haplotype carriers were all effective response to treatment,non-responders without this haplotype.Conclusion：These results suggest association between polymorphisms of CYP2D6 gene and ADHD better clinical improvement with atomoxetine treatment,it is worth further exploration in a large sample.

关 键 词：注意缺陷多动障碍 细胞色素酶 CYP2D6 托莫西汀 遗传相关性研究 

分 类 号：R749.94[医药卫生—神经病学与精神病学]