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Eur Child Adolesc Psychiatry (2010) 19:6774 DOI 10.1007/s00787-009-0043-6
ORIGINAL CONTRIBUTION
Adenosine A2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder
Christine M. Freitag Konstantin Agelopoulos Ellen Huy Matthias Rothermundt Petra Krakowitzky Jobst Meyer Jrgen Deckert Alexander von Gontard Christa Hohoff
Received: 14 November 2008 / Accepted: 10 June 2009 / Published online: 30 June 2009 Springer-Verlag 2009
Abstract Autism spectrum disorders (ASDs) are heterogeneous disorders presenting with increased rates of anxiety. The adenosine A2A receptor gene (ADORA2A) is associated with panic disorder and is located on chromo-some 22q11.23. Its gene product, the adenosine A2A
receptor, is strongly expressed in the caudate nucleus, which also is involved in ASD. As autistic symptoms are increased in individuals with 22q11.2 deletion syndrome, and large 22q11.2 deletions and duplications have been observed in ASD individuals, in this study, 98 individuals with ASD and 234 control individuals were genotyped for
eight single-nucleotide polymorphisms in ADORA2A. Nominal association with the disorder was observed for rs2236624-CC, and phenotypic variability in ASD symptoms was inuenced by rs3761422, rs5751876 and rs35320474. In addition, association of ADORA2A variants with anxiety was replicated for individuals with ASD. Findings point toward a possible mediating role of ADORA2A variants on phenotypic expression in ASD that need to be replicated in a larger sample.
Keywords Autism spectrum disorder ADORA2A
Anxiety Basal ganglia Caudate nucleus Glutamate
Introduction
Autism spectrum disorders (ASD) are genetically as well as phenotypically heterogeneous disorders, which are dened by qualitative impairments in social interaction and communication as well as stereotyped patterns of behavior and interests [2]. In addition to autism-specic impairments, high rates of anxiety disorders are observed [13]. ASD are predominately genetically determined disorders with a heritability of [90% [8]. Among several other chromosomal disorders, large deletions and duplications of chromosome 22q11.2 are observed in about 1% of individuals with ASD [16]. In individuals with chromosome 22q11 deletion syndrome, autistic symptoms are increased, with about 2050% meeting the diagnostic criteria of ASD [30]. Therefore, candidate genes in this region might either inuence the phenotypic expression and severity of ASD or might even be causal in their etiology. The adenosine A2A
receptor gene (ADORA2A) is located on 22q11.23. Studies in humans have shown an association of single variants in ADORA2A...