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Title: COMT Val158Met Polymorphism Modulates Huntington's Disease Progression
Author: Diego Balaguer, Ruth de
Schramm, Catherine
Rebeix, Isabelle
Dupoux, Emmanuel
Dürr, Alexandra
Brice, Alexis
Charles, Perrine
Cleret de Langavant, Laurent
Youssov, Katia
Verny, Christophe
Damotte, Vincent
Azulay, Jean-Philippe
Goizet, Cyril
Tranchant, Christine
Maison, Patrick
Rialland, Amandine
Schmitz, David
Jacquemot, Charlotte
Fontaine, Bertrand
Bachoud-Lévi, Anne-Catherine
Simonin, Clémence
French Speaking Huntington Group
Keywords: Corea de Huntington
Malalties del sistema nerviós
Lòbul frontal
Huntington's chorea
Nervous System Diseases
Frontal lobe
Issue Date: 22-Sep-2016
Publisher: Public Library of Science (PLoS)
Abstract: Little is known about the genetic factors modulating the progression of Huntington's disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington's Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression.
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It is part of: PLoS One, 2016, vol. 11, num. 9, p. e0161106
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Cognició, Desenvolupament i Psicologia de l'Educació)

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