Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder.
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.
Segman
R H
RH
Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. sronen@md2.huji.ac.il
Meltzer
A
A
Gross-Tsur
V
V
Kosov
A
A
Frisch
A
A
Inbar
E
E
Darvasi
A
A
Levy
S
S
Goltser
T
T
Weizman
A
A
Galili-Weisstub
E
E
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D016207:Cytokines / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007557:Israel; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats; D012306:Risk; D012795:Sialoglycoproteins / Q000235:genetics*
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins