title: Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families.
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 ADHD, 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.
authors.affiliation: Hospital Calvo Mackenna, Santiago, Chile.
authors.forename: Ximena
authors.initials: X
authors.lastname: Carrasco
authors.forename: Paula
authors.initials: P
authors.lastname: Rothhammer
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moraga
authors.forename: Hugo
authors.initials: H
authors.lastname: Henríquez
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Francisco
authors.initials: F
authors.lastname: Aboitiz
authors.forename: Francisco
authors.initials: F
authors.lastname: Rothhammer
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D002677:Chile; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4