Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder
Abstract
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability.(1) To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission.(2)Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons(3,4) and modulation of central monoaminergic reactivity.(5) We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism,(6) in a sample of 86 children with DSM-IV ADHD and their parents. Transmission disequilibrium analysis showed increased transmission of the IL-1Ra 4-repeat allele (chi(2) = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (chi(2) = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (chi(2) = 4.46, df 1, P = 0.035, RR = 1.292, 95% CI 1.01-1.66). The IL-1Ra 2-repeat allele was associated with a significantly decreased risk for ADHD (chi(2) = 4.65, df 1, P = 0.03, RR = 0.763, 95% CI 0.59-0.98). If replicated, this finding may point to a role for brain cytokine activity in the etiopathogenesis of ADHD.
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Genetic studies have found associations between polymorphisms in inflammatory pathway genes and ADHD.
“GWAS studies have identified associations between ADHD and the gene for IL-1RA (Segman et al., 2002) as well as genes involved in regulation of gene expression, cell adhesion, and inflammation (Zayats et al., 2015).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Segman et al., 2002
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Neuroinflammation as a risk factor for attention deficit hyperactivity disorder
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- Authors
- Segman, R. H., Meltzer, A., Gross-Tsur, V, Kosov, A., Frisch, A., Inbar, E., Darvasi, A., Levy, S., Goltser, T., Weizman, A., & Galili-Weisstub, E.
- Affiliations
- Hadassah Medical Center (IL)
- Tel Aviv University (IL)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Segman, R H
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2002-01-01
- Volume
- 7
- Issue
- 1
- Pages
- 72-74
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2005249939
- Cited by
- 68
- References
- 19
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hebrew University of Jerusalem
- 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 › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, interleukin-1 receptor antagonist, VNTR polymorphism, allele transmission, genetic susceptibility, brain cytokines, heritability, children
- MeSH terms
- Adolescent, Adult, Alleles, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Israel, Male, Risk, Sialoglycoproteins, Linkage Disequilibrium, Cytokines, Minisatellite Repeats, Genetic Predisposition to Disease, Interleukin 1 Receptor Antagonist Protein
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