No evidence for genetic association between DARPP-32 (PP1R1B) polymorphisms and attention deficit hyperactivity disorder
β Scribed by Nancy Laurin; Abel Ickowicz; Tejaswee Pathare; Molly Malone; Rosemary Tannock; Russell Schachar; James L. Kennedy; Cathy L. Barr
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 67 KB
- Volume
- 147B
- Category
- Article
- ISSN
- 1552-4841
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β¦ Synopsis
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 dopamineβ and cAMPβregulated phosphoprotein of relative molecular mass of 32 kDa (DARPPβ32) 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 DARPPβ32 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 DARPPβ32 gene in ADHD. Β© 2007 WileyβLiss, Inc.
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