Matthias Löhle1,2, Graziella Mangone3, Martin Wolz4, Bettina Beuthien-Baumann5,6,7, Liane Oehme5, Jörg van den Hoff6, Jörg Kotzerke5, Heinz Reichmann8, Jean-Christophe Corvol3, Alexander Storch1,2. 1. Department of Neurology, University of Rostock, Rostock, Germany. 2. German Centre for Neurodegenerative Diseases (DZNE) Standort Rostock, Rostock, Germany. 3. Sorbonne Université, INSERM UMRS1127 and CIC-1422, CNRS UMR7225, Assistance Publique Hôpitaux de Paris, ICM, Department of Neurology, Hôpital Pitié-Salpêtrière, Paris, France. 4. Department of Neurology, Elblandklinikum Meißen, Meissen, Germany. 5. Department of Nuclear Medicine, Technische Universität Dresden, Dresden, Germany. 6. Positron Emission Tomography Division, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 7. German Cancer Research Centre (DKFZ), Radiology, Heidelberg, Germany. 8. Department of Neurology, Technische Universität Dresden, Dresden, Germany.
Abstract
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 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. RESULTS: Patients carrying the MAOBCC/(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 MAOBTT/(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 MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications.
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 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PDpatients. RESULTS:Patients carrying the MAOBCC/(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 MAOBTT/(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 MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications.