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Cited by 21Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorPharmacogenetics and Drug Metabolism

Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis

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Yuan, Danfeng, Zhang, Manxue, Huang, Yan, Wang, Xinwei, Jiao, Jian, Huang, Yi·2021·Medicine
DOI 10.1097/md.0000000000027858PMC PMC8601359
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Abstract

Background: 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. Methods: 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. Results: 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, OR Tcarriers = 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). Conclusion: 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).

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Authors
Yuan, D., Zhang, M., Huang, Y., Wang, X., Jiao, J., & Huang, Y.
Affiliations
  • West China Hospital of Sichuan University (CN)
  • Sichuan University (CN)
  • Crestwood Preparatory College, Toronto, Canada.
Corresponding author
  • Huang, Yan
  • Huang, Yi
Venue
Medicine
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-11-19
Volume
100
Issue
46
Pages
e27858
ISSN
  • 0025-7974 (ISSN-L)
  • 1536-5964
DOI
10.1097/md.0000000000027858
PMC
PMC8601359
OpenAlex
W3212250322
Cited by
21
References
7
Citations by year
2026: 4 · 2025: 6 · 2024: 2 · 2023: 5 · 2022: 4
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Medicine (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
the natural science foundation of china (NO.81371495)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
attention deficit hyperactivity disorder, methylphenidate, pharmacogenomics, genetic polymorphism, treatment response, MspI polymorphism, hyperactive-impulsive symptoms, inattentive symptoms, children, candidate gene association, monoamine oxidase A
MeSH terms
Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Humans, Methylphenidate, Norepinephrine, Pharmacogenetics, Polymorphism, Genetic, Treatment Outcome, Receptors, Adrenergic, alpha-2, Norepinephrine Plasma Membrane Transport Proteins

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