科研之友
微信
新浪微博
Facebook
分享链接
摘要
Adenosine A(I) receptors (A(I)ARs) and the interacting adenosine A(2)A receptors are implicated in neurological and psychiatric disorders. Variants within the corresponding genes ADORAI and ADORA2A were shown associated with pathophysiologic alterations, particularly increased anxiety. It is unknown so far, if these variants might modulate the A(I)AR distribution and availability in different brain regions. In this pilot study, the influence of ADORAI and ADORA2A variants on in vivo AAR binding was assessed with the A(I)AR-selective positron emission tomography (PET) radioligand [F-18]CPFPX in brains of healthy humans. Twenty-eight normal control subjects underwent PET procedures to calculate the binding potential BPND of [F-18]CPFPX in cerebral regions and to assess ADORAI and ADORA2A single nucleotide polymorphism (SNP) effects on regional MIND data. Our results revealed SNPs of both genes associated with [F-18]CPFPX binding to the AAR. The strongest effects that withstood even Bonferroni correction of multiple SNP testing were found in nonsmoking subjects (N =22) for ADORA2A SNPs rs2236624 and rs5751876 (corr. P-all %26lt;0.05). SNP alleles previously identified at risk for increased anxiety like the rs5751876 T-allele corresponded to consistently higher A(I)AR availability in all brain regions. Our data indicate for the first time that variation of A(I)AR availability was associated with ADORA SNPs. The finding of increased A(I)AR 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.
- 出版日期2014-12
