Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients
Abstract
Aims Methylphenidate (MPH) is the most frequently prescribed drug in Attention Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter gene has been studied in MPH-response and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters. We aimed to analyze this monoamine transporter gene in relation to ADHD per se and MPH-response in particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian sample. Methods Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children (age: 9.3±2.6; 86.5% male) using ADHD-RS hyperactivity-impulsivity and inattention scales. For case-control analysis 486 control subjects were also genotyped. At the MPH-response analysis responders had minimum 25% decrease of ADHD-RS total score after 2months of treatment, and chi-square test compared 90 responders and 32 non-responders, whereas ANOVA was used to assess symptom improvement after the first month among the 122 ADHD patients. Results The classical case-control analysis did not yield any association with ADHD diagnosis, which was supported by meta-analysis conducted on the available genetic data (combining previously published and the present studies). On the other hand, the intronic rs3785143 showed nominal association with inattention symptoms (p=0.01). T…
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Several biological pathways have been suggested to potentially affect MPH mechanisms through patient genotype, mostly concerning monoamine pathways.
“several biological pathways have been suggested to potentially affect MPH mechanisms through patient genotype, mostly concerning monoamine pathways [43–48].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [44]
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
- Authors
- Angyal, N., Horvath, E. Z., Tarnok, Z., Richman, M. J., Bognar, E., Lakatos, K., Sasvari-Szekely, M., & Nemoda, Z.
- Affiliations
- Semmelweis University (HU)
- Eötvös Loránd University (HU)
- Institute of Cognitive Neuroscience and Psychology (HU)
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 84
- Issue
- Pt A
- Pages
- 122-128
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2791741161
- Cited by
- 25
- References
- 4
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Funders
- Hungarian Scientific Research Fund (OTKA F67784)
- 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
- norepinephrine transporter, methylphenidate response, attention deficit hyperactivity disorder, pharmacogenetics, single nucleotide polymorphisms, promoter polymorphism, haplotype analysis, inattentive symptoms, hyperactivity/impulsivity, monoamine transporters, children
- MeSH terms
- Pharmacogenomic Variants, Central Nervous System Stimulants, Attention, Attention Deficit Disorder with Hyperactivity, Child, Female, Haplotypes, Humans, Introns, Male, Methylphenidate, Promoter Regions, Genetic, Linkage Disequilibrium, Case-Control Studies, Polymorphism, Single Nucleotide, Norepinephrine Plasma Membrane Transport Proteins, Genetic Association Studies
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