Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families
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Date
2006
Journal Title
Journal ISSN
Volume Title
Publisher
WILEY
Abstract
Attention-deficit/hyperactivity disorder, ADHD [MIM 126452], is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. As part of an ongoing study of AMID, we carried out a family-based discordant sib-pair analysis to detect possible associations between dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms and ADHD in Chilean families. Both loci individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DAT1 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings (Fisher's exact test P > 0.25 in both cases). However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DAT1 10 allele homozygosity were significantly higher (34.6%) in cases (26), compared with their unaffected siblings (25) (4%; Fisher's exact test P = 0.0096; odds-ratio, OR = 12.71). Increased density of dopamine transporter in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of further incisive studies. (C) 2005 Wiley-Liss, Inc.
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Keywords
DRD4, DAT1, genotypic interaction, ADHD, association with (?), DEFICIT HYPERACTIVITY DISORDER, DOPAMINE-D4 RECEPTOR GENE, DIAGNOSTIC-CRITERIA, TRANSPORTER GENE, TEACHER RATINGS, 7-REPEAT ALLELE, ASSOCIATION, ADHD, POLYMORPHISM, PREVALENCE