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.

Association Between DARPP-32 Gene Polymorphism and Personality Traits in Healthy Chinese-Han Subjects

“…Decreased DARPP-32 protein levels have been observed in the postmortem dorsolateral prefrontal cortex of schizophrenia patients (Albert et al 2002). Other studies, however, did not support a major contribution of DARPP-32 to bipolar disorders (Yoshimi et al 2008), schizophrenia (Li et al 2006;Hu et al 2007;Yoshimi et al 2008), or attention deficit hyperactivity disorder (Laurin et al 2008). Although DARPP-32 has received considerable attention in both basic and clinical neuropsychiatric studies, data demonstrating the association between DARPP-32 alleles and distinct personality traits are almost wholly lacking.…”