Abstract
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Objectives The methylation of cytosine nucleotids in the CpG islands is a relevant mode of epigenetic modulation of biofunctions. The rate of CpG methylation in a pioneering work of Shumay et al. (2012) was already shown to be associated with [11C]clorgyline binding in positron emission tomography. Since MAOA is involved in the metabolism of catecholamines including dopamine its possible impact on the dopaminergic release and turn-over and subsequent effects on behavior is a relevant issue. Therefore the present investigation compares the rate of methylation of MAOA-CpG islands with the individual extent of striatal dopamine synthesis capacity (K) and the rates of desamination (kloss).
Methods Thirty healthy male subjects were included after informed consent. They agreed into MAOA VNTR promotor polymorphism characterization followed by a peripheral analysis of the methalytion rate of 14 CpG islands in the MAOA gene. Subjects underwent a single [18F]FDOPA-PET scan and an MR-scan for coregistration and normalisation. [18F]FDOPA scans were generally acquired for 124min and analysed according to the reversible inlet/outlet model obtaining the net blood/brain clearance (dopamine synthesis capacity, K), the loss of metabolites (dopaminergic turn-over, kloss), and the total distribution volume (Vd).
Results The overall methylation of all CpG islands had an extent of 67.0% (SD: 6.7%) and showed an association with the caudate net blood/brain uptake (K) of [18F]FDOPA between 0.387 (p=0.022) in the right CN. The putamen values showed trend-level significance. In particular, CpG islands 1, 6 and 7 showed methylation rates that prominently correlated with striatal K parameters. For the association between the right ventral CN, this association survived Bonferroni-correction (r=0.552; p<0.001). Also kloss showed positive associations on somewhat lower extent (entire methylation state vs: right ventral CN: r=0.355, p=0.037).
Conclusions The high association between epigenetic parameters of the MAOA-gene (the VNTR-polymorphism of which usually shows only little impact on FDOPA kinetics) strengthen the possible relevance of these pathways on the modulation of human behaviour. It is in line with the previously published association to [11C]clorgyline binding studies.