Coexpression of Gene Transcripts with Monoamine Oxidase A Quantified by Human In Vivo Positron Emission Tomography.
The monoamine oxidase A (MAO-A) is integral to monoamine metabolism and is thus relevant to the pathophysiology of various neuropsychiatric disorders however, associated gene-enzyme relations are not well understood. This study aimed to unveil genes coexpressed with MAO-A. Therefore, 18 179 mRNA expression maps (based on the Allen Human Brain Atlas) were correlated with the cerebral distribution volume (VT) of MAO-A assessed in 36 healthy subjects (mean age ± standard deviation 32.9 ± 8.8 years, 18 female) using 11Charmine positron emission tomography scans. Coexpression analysis was based on Spearmans ρ, over-representation tests on Fishers exact test with false discovery rate (FDR) correction. The analysis revealed 35 genes in cortex (including B-cell translocation gene family, member 3, implicated in neuroinflammation) and 247 genes in subcortex (including kallikrein-related peptidase 10, implicated in Alzheimers disease). Significantly over-represented Gene Ontology terms included neuron development, neuron differentiation, and cell-cell signaling as well as axon and neuron projection. In vivo MAO-A enzyme distribution and MAOA expression did not correlate in cortical areas (ρ 0.08) while correlation was found in subcortical areas (ρ 0.52), suggesting influences of region-specific post-transcriptional and -translational modifications. The herein reported information could contribute to guide future genetic studies, deepen the understanding of associated pathomechanisms and assist in the pursuit of novel therapeutic targets.