| Summary |
They investigated the role of interleUnited Kingdomin-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 (P=0.04) and decreased transmission of the 2-repeat allele (P=0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (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 (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. |
| Total Sample |
86 children with ADHD and their parents were studies. Of these, 85 children and 134 parents from 76 families, were included in the haplotype-based haplotype relative risk (HHRR) analysis, employed for relative risk calculations, and 58 children from 49 families, and 63 informative parents, were available for the TDT analysis. |
| Sample Collection |
Probands were ascertained through the Child Neurology clinic at Share Zedek Medical Center, and the Child Psychiatric clinics at the Hadassah Medical Center, and TiratCarmel hospital. Children thought to have ADHD and their consenting biological parents were entered into the study assessment protocol. Eighty-six children with ADHD and their biological parents were recruited. Of these, 58 were independent triads, nine had two affected children, and 19 were diads. The study was approved by the Internal Review Board (Helsinki Committee) of the Hadassah-Hebrew University Medical Center and all subjects gave written informed consent. |
| Diagnosis Description |
Subjects met DSM-IV criteria for one of the three subtypes of ADHD (inattentive, hyperactive-impulsive, or combined). Subjects underwent medical and neurological and psychiatric evaluation and were excluded if they had a history of neurological or chronic medical illness, affective or psychotic disorder, Tourette's syndrome, or pervasive developmental disorder. Subjects were excluded if they scored below 85 on both the performance and verbal scales, or the full Wechsler Intelligence Scale for Children, 3rd edition, or attended special schooling. Information from parents was obtained through semi-structured interviews, aided by the Conners Parent and Teacher Rating Scales Revised. Children were assessed using the Kidi-Schedule for Affective Disorders and Schizophrenia (K-SADS) questionnaire, and a DSM-IV item Checklist of ADHD. |
| Technique |
DNA was extracted from fresh whole blood samples anticoagulated with EDTA, using Boehringer Mannheim DNA extraction kits for mammalian blood (Mannheim, Germany). The IL-1Ra intron 2 VNTR was genotyped as previously described. |
| Analysis Method |
TDT analysis was performed using the TDT-STDT Program 1.1 available from the Spielman lab site. Haplotype-based haplotype relative risk (HHRR) was calculated according to Terwilliger and Ott. |
| Result Description |
Transmission disequilibrium analysis showed significant evidence for biased transmission of the two frequent IL-1Ra VNTR alleles in current sample. Increased transmission was observed for the 4-repeat allele. Of 71 informative transmissions, the 4-repeat allele was passed 44 times to affected children, compared with 27 times that it was not passed (P=0.04). Decreased transmission was observed for the 2-repeat allele. Of 63 informative transmissions, the 2-repeat allele was passed 23 times to affected children, compared with 40 times that it was not passed (P=0.03). The IL-1Ra 4-repeat allele was associated with a significantly increased risk for ADHD (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 (P=0.03, RR=0.763, 95% CI 0.59-0.98). |
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