Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
Crestwood Preparatory College, Toronto, Canada.
Medicine (Baltimore). 2021 Nov 19;100(46):e27858. doi: 10.1097/MD.0000000000027858.
Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.
Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.
This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).
Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).
注意缺陷多动障碍（ADHD）是最常见的儿童期起病的神经发育障碍，而哌醋甲酯（MPH）被认为是 ADHD 的一线药物之一。不幸的是，这种药物仅对一些 ADHD 儿童有效。本荟萃分析旨在评估去甲肾上腺素能基因多态性是否影响 ADHD 儿童 MPH 的疗效。
通过在 PubMed、Web of Science 和 Embase 上进行文献检索，确定截至 2020 年 3 月 1 日发表的英文候选基因研究。根据个体临床试验的数据汇总情况，考虑 MPH 药物基因组学。根据异质性，应用固定效应或随机效应模型计算比值比和均数差值。
本荟萃分析包括 15 项研究和 1382 名患者。选择 NET 基因（rs5569、rs28386840、rs2242446、rs3785143）的 4 个多态性和α2A-肾上腺素能受体基因（ADRA2A）的 2 个多态性（MspI 和 DraI）进行分析。在所有研究的汇总数据中，rs28386840 多态性的 T 等位基因携带者对 MPH 的反应明显更敏感（P < 0.001，ORTcarriers = 2.051，95%置信区间[CI]：1.316，3.197），且与多动冲动症状改善具有显著相关性（P < 0.001，均数差值：1.70，95% CI：0.24，3.16）。ADRA2A 多态性与 MPH 反应整体无显著相关性。然而，MspI 多态性的 G 等位基因携带者与注意力不集中症状的显著改善相关（P < 0.001，均数差值：0.31，95% CI：0.15，0.47）。
本荟萃分析结果表明，去甲肾上腺素能基因多态性可能影响 MPH 的反应。NET rs28386840 与 ADHD 儿童 MPH 反应的改善有关。ADRA2A MspI 与注意力不集中症状的改善有关。需要进一步进行更大样本的研究来验证这些结果。注册：PROSPERO（编号：CRD42021265830）。
