Huang Hui-Ching, Wu Lawrence Shih-Hsin, Yu Shun-Chieh, Wu Bo-Jian, Lua Ahai Chang, Lee Shin-Min, Liu Chao-Zong
Department of Pharmacy, Yuli Hospital, Ministry of Health and Welfare, Hualien, Taiwan.
Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Psychiatry Investig. 2018 Mar;15(3):306-312. doi: 10.30773/pi.2017.07.24. Epub 2018 Feb 28.
The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP.
The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis.
Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64-627.80).
The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.
哌醋甲酯（MPH）治疗注意力缺陷多动障碍（ADHD）的疗效与α-2A肾上腺素能受体（ADRA2A）基因-1291C/G单核苷酸多态性（SNP）有关。我们研究了MPH治疗台湾儿童和青少年ADHD的效果及其与ADRA2A基因-1291C/G SNP的关系。
符合DSM-IV ADHD诊断标准的受试者经历一个滴定期以确定维持治疗的MPH剂量。经过4周的维持治疗后，通过斯旺森、诺兰和佩勒姆第四版总分评估MPH的疗效。得分降低超过25%的受试者被视为反应者，改善≥50%的受试者被视为更好的反应者。通过DNA测序鉴定ADRA2A基因的-1291C/G变异，并通过二元逻辑回归分析检查其与MPH反应的相关性。
59名受试者中，44名（74.6%）对MPH治疗有反应，且反应性与ADRA2A基因-1291C/G SNP无关。将反应性受试者分为中度反应者和更好的反应者并进行统计分析后，GG纯合子对MPH治疗有更好反应的可能性高于CC纯合子（p=0.02），优势比为32.14（95%CI=1.64-627.80）。
ADRA2A基因-1291C/G SNP与MPH治疗台湾儿童和青少年ADHD的疗效相关。携带纯合-1291G等位基因的反应性受试者对MPH治疗更可能有更好的反应。
