title: Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain.
abstract: Adenosine A1 receptors (A1ARs) and the interacting adenosine A2A receptors are implicated in neurological and psychiatric disorders. Variants within the corresponding genes ADORA1 and ADORA2A were shown associated with pathophysiologic alterations, particularly increased anxiety. It is unknown so far, if these variants might modulate the A1AR distribution and availability in different brain regions. In this pilot study, the influence of ADORA1 and ADORA2A variants on in vivo A1AR binding was assessed with the A1AR-selective positron emission tomography (PET) radioligand [(18)F]CPFPX in brains of healthy humans. Twenty-eight normal control subjects underwent PET procedures to calculate the binding potential BPND of [(18)F]CPFPX in cerebral regions and to assess ADORA1 and ADORA2A single nucleotide polymorphism (SNP) effects on regional BPND data. Our results revealed SNPs of both genes associated with [(18)F]CPFPX binding to the A1AR. The strongest effects that withstood even Bonferroni correction of multiple SNP testing were found in non-smoking subjects (N=22) for ADORA2A SNPs rs2236624 and rs5751876 (corr. Pall<0.05). SNP alleles previously identified at risk for increased anxiety like the rs5751876 T-allele corresponded to consistently higher A1AR availability in all brain regions. Our data indicate for the first time that variation of A1AR availability was associated with ADORA SNPs. The finding of increased A1AR availability in regions of the fear network, particularly in ADORA2A risk allele carriers, strongly warrants evaluation and replication in further studies including individuals with increased anxiety.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Hohoff
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Garibotto
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Elmenhorst
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Baffa
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Kroll
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Alana
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwarte
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.affiliation: Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000235:genetics; D058915:Purinergic P1 Receptor Antagonists / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000378:metabolism*; D014970:Xanthines / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014970:Xanthines; D019788:Fluorodeoxyglucose F18