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Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain

Hohoff, Christa
Elmenhorst, David
Baffa, Anna
Kroll, Tina
Hoffmann, Alana
Schwarte, Kathrin
Zhang, Weiqi
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Published in Neuropsychopharmacology. 2014, vol. 39, no. 13, p. 2989-99
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.
Keywords AdultBrain/diagnostic imaging/drug effects/metabolismFemaleFluorodeoxyglucose F18/pharmacokineticsGenetic LinkageGenotypeHumansMagnetic Resonance ImagingMaleMiddle AgedPolymorphism, Single Nucleotide/geneticsPositron-Emission TomographyProtein Binding/geneticsPurinergic P1 Receptor Antagonists/pharmacokineticsReceptor, Adenosine A1/genetics/metabolismReceptor, Adenosine A2A/genetics/metabolismXanthines/pharmacokineticsYoung Adult
PMID: 24943643
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Research group Laboratoire de neuroimagerie et de traceurs moléculaires innovants (984)
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HOHOFF, Christa et al. Association of adenosine receptor gene polymorphisms and in vivo adenosine A1 receptor binding in the human brain. In: Neuropsychopharmacology, 2014, vol. 39, n° 13, p. 2989-99. doi: 10.1038/npp.2014.150 https://archive-ouverte.unige.ch/unige:94193

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Deposited on : 2017-05-11

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