Julia Muellner1, Iman Gharrad2, Marie-Odile Habert3, Aurélie Kas3, Jean-Baptiste Martini4, Florence Cormier-Dequaire5, Khadija Tahiri2, Marie Vidailhet5, Niklaus Meier1, Alexis Brice2, Michael Schuepbach1, Alain Mallet6, Andreas Hartmann5, Jean-Christophe Corvol7. 1. Department of Neurology, Inselspital, Freiburgstrasse 100, 3010 Bern, Switzerland; Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France. 2. Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France. 3. AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC Paris 06, CNRS UMR 7371, INSERM U1146, 75013 Paris, France. 4. AP-HP, Department of Nuclear Medicine, Pitié-Salpêtrière Hospital, Sorbonne University, UPMC Paris 06, CNRS UMR 7371, INSERM U1146, 75013 Paris, France; Centre d'Analyse et de Traitement des Images (CATI), 75013 Paris, France. 5. Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France; AP-HP, Department of Neurology, Pitié-Salpêtrière Hospital, 75013 Paris, France. 6. Inserm U436, Laboratory of Mathematical and Statistical Modelisation in Biology and Medicine, Pitié-Salpêtrière Hospital, 91 bd de l'hôpital, 75634 Paris Cedex 13, France; APHP, Clinical Research Unit, Department of Biostatistics, Pitié-Salpêtrière Hospital, 75013 Paris, France. 7. Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France; AP-HP, Department of Neurology, Pitié-Salpêtrière Hospital, 75013 Paris, France. Electronic address: jean-christophe.corvol@psl.aphp.fr.
Abstract
BACKGROUND: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. METHODS: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. RESULTS: 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 intermediate metabolizers showed significantly higher rates of striatal denervation (COMT(HL+LL) BP = 1.32 ± 0.04) than high metabolizers (COMT(HH), BP = 1.6 ± 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender-genotype interaction. CONCLUSIONS: Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms.
RCT Entities:
BACKGROUND: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 PDpatients according to COMT rs4680 genotype. METHODS: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. RESULTS: 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 intermediate metabolizers showed significantly higher rates of striatal denervation (COMT(HL+LL) BP = 1.32 ± 0.04) than high metabolizers (COMT(HH), BP = 1.6 ± 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender-genotype interaction. CONCLUSIONS: Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms.
Authors: Erinaldo Ubirajara Damasceno Dos Santos; Isaura Isabelle Fonseca Gomes da Silva; Amdore Guescel C Asano; Nadja Maria Jorge Asano; Maria De Mascena Diniz Maia; Paulo Roberto Eleutério de Souza Journal: Mol Biol Rep Date: 2020-11-05 Impact factor: 2.316
Authors: Ismael Huertas; Silvia Jesús; Francisco Javier García-Gómez; José Antonio Lojo; Inmaculada Bernal-Bernal; Marta Bonilla-Toribio; Juan Francisco Martín-Rodriguez; David García-Solís; Pilar Gómez-Garre; Pablo Mir Journal: PLoS One Date: 2017-04-11 Impact factor: 3.240