Objective: To examine the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover estimated as the inverse of the effective dopamine distribution volume ratio (EDVR) by ¹⁸F-dopa PET in de novo Parkinson disease (PD).

Background: We have recently shown that baseline putaminal dopamine turnover in de novo PD predicts the risk for later motor complications. However, it remains unclear which factors determine putaminal dopamine turnover in individual patients.

Methods: In this retrospective, observer-blinded cohort study, we compared the striatal ¹⁸F-dopa uptake (K_occ) and the effective distribution volume ratio (EDVR) as the inverse of dopamine turnover using quantitative ¹⁸F-dopa PET imaging in 29 patients with de novo untreated PD with respect to common functional polymorphisms in genes involved in dopamine metabolism. Four candidate variants were selected from the MAOB (rs1799836), COMT (rs4680), DAT (VNTR) and DDC (rs921451) genes.

Results: Mean striatal K_occ values (caudate nucleus and putamen) did not significantly differ between variants of the four genes. Patients carrying the MAOB^CC/(C)/CT genotypes (known to be associated with low/intermediate enzyme activity in brain) had a higher mean putaminal EDVR (lower dopamine turnover) compared to patients with the MAOB^TT/(T) genotypes (associated with high enzyme activity in the brain) (mean relative difference: 13.6% [95%CI: 6.0% to 21.3%]; unadjusted p=0.001, unpaired two-sided t-test). Adjustment for age and disease severity using the UPDRS Part III confirmed the difference in mean putaminal EDVR (F=10.868, p=0.003) between the MAOB alleles. Mean EDVRs of the caudate nucleus region did not show differences. In addition, we did not observe significant associations of K_occ and EDVR values and genetic variants for the remaining genes.

Conclusions: The MAOB rs1799836 polymorphism predicts putaminal dopamine turnover in early PD with the MAOB^TT/(T) genotypes (linked to high enzyme activity in brain tissue) leading to higher disease-induced dopamine turnover, which has recently shown to be associated with an increased risk for later motor complications. Individual assessment of this polymorphism might therefore be helpful for early risk stratification in PD patients with respect to motor complications.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-maob-gene-intron-13-polymorphism-predicts-putaminal-dopamine-turnover-in-de-novo-parkinsons-disease/