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. 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.