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

摘要

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.%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。