Journal
MOVEMENT DISORDERS
Volume 33, Issue 9, Pages 1496-1501Publisher
WILEY
DOI: 10.1002/mds.27466
Keywords
dopamine metabolism; positron emission tomography (PET); dopamine turnover; monoamine oxidase B (MAOB); functional gene polymorphisms; Parkinson's disease
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Funding
- Pfizer Pharma, Berlin, Germany
- program Investissements d'Avenir [ANR-10-IAIHU-06]
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Objective: The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). Methods: This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on F-18-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by F-18-fluorodopa PET in 28 untreated PD patients. Results: Patients carrying the MAOB(CC/(C)/CT) genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOB(TT/(T)) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. Conclusions: The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOB(TT) allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. (C) 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
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