TY - JOUR
T1 - Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder
AU - Segman, R. H.
AU - Meltzer, A.
AU - Gross-Tsur, V.
AU - Kosov, A.
AU - Frisch, A.
AU - Inbar, E.
AU - Darvasi, A.
AU - Levy, S.
AU - Goltser, T.
AU - Weizman, A.
AU - Galili-Weisstub, E.
N1 - Funding Information:
AD and EI are supported by a FIRST grant of the Israeli Academy of Science.
PY - 2002
Y1 - 2002
N2 - Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability. To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission. Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons and modulation of central monoaminergic reactivity. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism, 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 (χ2 = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (χ2 = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (χ2 = 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 (χ2 = 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.
AB - Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability. To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission. Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons and modulation of central monoaminergic reactivity. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism, 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 (χ2 = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (χ2 = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (χ2 = 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 (χ2 = 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.
KW - ADHD
KW - Attention deficit hyperactivity disorder
KW - Interleukin-1 receptor antagonist gene
KW - Transmission disequilibrium test
UR - http://www.scopus.com/inward/record.url?scp=85047699517&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4000919
DO - 10.1038/sj.mp.4000919
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AN - SCOPUS:85047699517
SN - 1359-4184
VL - 7
SP - 72
EP - 74
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 1
ER -