title: No evidence for genetic association between DARPP-32 (PP1R1B) polymorphisms and attention deficit hyperactivity disorder.
abstract: Attention deficit hyperactivity disorder (ADHD) has a strong genetic basis, and evidence from human and animal studies suggests that a dopamine system dysfunction plays a role in the disorder pathophysiology. Several genes involved in dopamine neurotransmission have shown replicated genetic association with ADHD. These include the dopamine receptors D4 (DRD4), D5 (DRD5), and the dopamine transporter (DAT1) genes. Recently, evidence has also accumulated in favor of the dopamine receptor D1 gene (DRD1). The dopamine- and cAMP-regulated phosphoprotein of relative molecular mass of 32 kDa (DARPP-32) is a key component of dopamine signaling, acting as a converging point for several neurotransmitter systems influencing dopaminergic neurons and regulating a wide variety of downstream effectors. Here, we tested the DARPP-32 gene, PPP1R1B, for association with ADHD using four polymorphic markers selected across the gene in a sample of 255 ADHD families. We did not detect evidence of association of individual marker alleles and haplotype analysis did not reveal significant association in this sample of families. Moreover, we found no relationship between the same alleles or haplotypes and symptom scores of inattention or hyperactivity/impulsivity in these families using a quantitative approach. In conclusion, albeit a key regulatory role in dopamine signaling, our data do not support a major contribution of the DARPP-32 gene in ADHD.
authors.affiliation: Division of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Laurin
authors.forename: Abel
authors.initials: A
authors.lastname: Ickowicz
authors.forename: Tejaswee
authors.initials: T
authors.lastname: Pathare
authors.forename: Molly
authors.initials: M
authors.lastname: Malone
authors.forename: Rosemary
authors.initials: R
authors.lastname: Tannock
authors.forename: Russell
authors.initials: R
authors.lastname: Schachar
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
mesh_terms: D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human