Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson's disease

Parkinsonism & Related Disorders
Julia MuellnerJean-Christophe Corvol

Abstract

Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met, COMT(LL)). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype. Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was defined by the ratio of tracer-binding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan(®) SNP genotyping assay. We used a regression model to evaluate the effect of COMT genotype on the BP in the striatum and its sub-regions. Genotype distribution was: 11 (27.5%) COMT(HH), 26 (65%) COMT(HL) and 3 (7.5%) COMT(LL). There were no significant differences in disease severity, treatments, or motor scores between genotypes. When adjusted to clinical severity, gender and age, low and interme...Continue Reading

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Citations

Mar 27, 2018·Journal of Clinical Pharmacology·Tiago Furtado SampaioPaulo Roberto Eleutério de Souza
May 19, 2018·Annals of Nuclear Medicine·Kyoungjune PakIn Joo Kim
Sep 28, 2017·The International Journal of Neuroscience·Victor MarinhoSilmar Teixeira
May 19, 2017·Frontiers in Aging Neuroscience·Jing-Ya LinZhen-Guo Liu
Nov 6, 2020·Molecular Biology Reports·Erinaldo Ubirajara Damasceno Dos SantosPaulo Roberto Eleutério de Souza
Mar 23, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Rahul GauravStéphane Lehéricy

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