Cited by 193Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

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Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD)

McCracken, J T, Smalley, S L, McGough, J J, Crawford, L, Del'Homme, M, Cantor, R M, Liu, A, Nelson, S F·2000·Molecular Psychiatry

DOI 10.1038/sj.mp.4000770

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Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.

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Dedication
(2018) · Oxford University Press eBooks · doi:10.1093/med/9780190884574.002.0004
Fatores ambientais e genéticos associados ao transtorno de déficit de atenção/hiperatividad tipo desatento : Avaliação de fumo na gestão e genes dopaminérgicos e noradrenérgicos
Schmitz, M. D. (2005) · Americanae (AECID Library)
BindingDB Entry 50035271: Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine receptor binding and ligand efficacy.
BindingDB (2012) · UC San Diego · doi:10.7270/q2jm2b5x
BindingDB Entry 50035155: Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179).
BindingDB (2012) · UC San Diego · doi:10.7270/q27p8zwz
BindingDB Entry 50037726: 2-[(4-phenylpiperazin-1-yl)methyl]imidazo(di)azines as selective D4-ligands. Induction of penile erection by 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]imidazo[1,2-a]pyridine (PIP3EA), a potent and selective D4 partial agonist.
BindingDB (2012) · UC San Diego · doi:10.7270/q20g3kz5
BindingDB Entry 50035236: 2,4-Disubstituted pyrroles: synthesis, traceless linking and pharmacological investigations leading to the dopamine D4 receptor partial agonist FAUC 356.
BindingDB (2012) · UC San Diego · doi:10.7270/q2t72j0v
BindingDB Entry 50018897: Discovery of 3-methyl-N-(1-oxy-3',4',5',6'-tetrahydro-2'H-[2,4'-bipyridine]-1'-ylmethyl)benzamide (ABT-670), an orally bioavailable dopamine D4 agonist for the treatment of erectile dysfunction.
BindingDB (2009) · UC San Diego · doi:10.7270/q25x28mm
BindingDB Entry 50035359: Cyclic amidines as benzamide bioisosteres: EPC synthesis and SAR studies leading to the selective dopamine D4 receptor agonist FAUC 312.
BindingDB (2012) · UC San Diego · doi:10.7270/q26t0n5v

Authors: McCracken, J. T., Smalley, S. L., McGough, J. J., Crawford, L., Del'Homme, M., Cantor, R. M., Liu, A., & Nelson, S. F.
Affiliations: University of California, Los Angeles (US)
Corresponding author: McCracken, J T
ORCID: McCracken, J T
Smalley, S L
McGough, J J
Cantor, R M
Liu, A
Nelson, S F
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2000-09-01
Volume: 5
Issue: 5
Pages: 531-536
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/sj.mp.4000770
OpenAlex: W1987273630
Cited by: 189
References: 39
Citations by year: 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 17 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 2 · 2013: 4 · 2012: 9
FWCI: 7.44
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (MH 58277, R01MH058277)
National Center for Research Resources (P41 RR 03655, P41RR003655)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: attention deficit hyperactivity disorder, dopamine D4 receptor, DRD4, promoter polymorphism, linkage, transmission disequilibrium test, genetic susceptibility, children
MeSH terms: Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Exons, Family Health, Female, Haplotypes, Humans, Male, Polymorphism, Genetic, Linkage Disequilibrium, Receptors, Dopamine D2, Tandem Repeat Sequences, Receptors, Dopamine D4

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Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD)

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