Abstract
Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness.To search for possible associations between dopamine receptor D4 (DRD4) and dopamine transponder 1 (DATl) polymorphisms and ADHD in Chilean families.We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV criteria and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls.Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5%) in cases (40), compared with (2.8%) unaffected siblings (36), with an odds-ratio of 10.16.The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters 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 studies to understand the functional basis of ADHD.
Highlights
Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness
Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV criteria and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls
Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function
Summary
Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Estudios recientes han revelado que al menos dos polimorfismos genéticos del sistema dopaminérgico, un receptor y un transportador (DRD4/7 y DAT1/10), están asociados al síndrome de déficit atencional con hiperactividad (SDAH)[1,2,3]. La frecuencia de presentación de estos alelos en Santiago de Chile es intermedia entre los valores obtenidos en poblaciones europeas e indígenas, como era de esperar considerando su composición genética[4]. Posteriormente, en un análisis diferente, que comprendió el estudio de la asociación conjunta de genotipos de los mismos genes con el SDAH, obtuvimos como resultado una asociación altamente significativa de los genotipos heterocigoto del gen DRD4/7 y homocigoto del gen DAT1/10. Esta comunicación tiene por objetivo dar a conocer y discutir los nuevos resultados
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