ArticleProceedings of the National Academy of Sciences of the United States of America2006
A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03154359 (An Open-Label, Single- and Multi-Dose Study to Evaluate the Relationship Between the Pharmacokinetics, Pharmacodynamics, and Clinical Outcomes of Atomoxetine in CYP2D6 Extensive, Intermediate and Poor Metabolizers in Children With Attention Deficit/Hyperactivity Disorder), which is not on this map. Cited by 61 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Single- and Multi-Dose Study to Evaluate the Relationship Between the Pharmacokinetics, Pharmacodynamics, and Clinical Outcomes of Atomoxetine in CYP2D6 Extensive, Intermediate and Poor Metabolizers in Children With Attention Deficit/Hyperactivity Disorder
Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 155 citations in OpenAlex.
- Meta-Analysis: Hemodynamic Responses to Sub-anesthetic Doses of Ketamine in Patients With Psychiatric Disorders.Frontiers in psychiatry · 2021Pooled it
- Candidate gene studies of ADHD: a meta-analytic review.Human genetics · 2009Pooled it
- Ketamine influences the locus coeruleus norepinephrine network, with a dependency on norepinephrine transporter genotype - a placebo controlled fMRI study.NeuroImage. Clinical · 2018Trial
- Factors Influencing the Cardiovascular Response to Subanesthetic Ketamine: A Randomized, Placebo-Controlled Trial.The international journal of neuropsychopharmacology · 2017Trial
- Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans.Molecular psychiatry · 2009Trial
- Rats and humans paying attention: cross-species task development for translational research.Neuropsychology · 2008Trial
- Inverse Association of Locus Coeruleus MRI Integrity With Structural Volume and Its Impact on Individual's Inattentiveness.Human brain mapping · 2025Article
- Review
- The Role of Gene-Gene Interaction BetweenChildren (Basel, Switzerland) · 2025Article
- Current Perspectives on Attention-deficit Hyperactivity Disorder.Current molecular medicine · 2025Review
- Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events.Nature communications · 2024Article
- Noradrenergic gene variation shaping vulnerability and resilience by affecting mental health-related characteristics: A systematic review.Neuroscience applied · 2024Article
- Noradrenaline tracks emotional modulation of attention in human amygdala.Current biology : CB · 2023Article
- Neural Correlates of Impaired Cognitive Control in Individuals with Methamphetamine Dependence: An fMRI Study.Brain sciences · 2023Article
- The Association between Executive Functions and Body Weight/BMI in Children and Adolescents with ADHD.Brain sciences · 2021Article
- I-123 metaiodobenzylguanidine innervation imaging as a tool for norepinephrine transporter research: A possible application for genetic analysis in heart failure.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2018Article
- Differential Genetic Effect of the Norepinephrine Transporter Promoter Polymorphisms on Attention Problems in Clinical and Non-clinical Samples.Frontiers in neuroscience · 2018Article
- Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects.Scientific reports · 2017Article
- Role of GNB3, NET, KCNJ11, TCF7L2 and GRL genes single nucleotide polymorphism in the risk prediction of type 2 diabetes mellitus.3 Biotech · 2016Review
- Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters.Pharmacological reviews · 2016Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention-deficit hyperactivity disorder and other neuropsychiatric diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.