Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson’s disease
Identifieur interne : 000332 ( Hal/Corpus ); précédent : 000331; suivant : 000333Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson’s disease
Auteurs : Julia Muellner ; Iman Gharrad ; Marie-Odile Habert ; Aurélie Kas ; Jean-Baptiste Martini ; Florence Cormier-Dequaire ; Khadija Tahiri ; Marie Vidailhet ; Niklaus Meier ; Alexis Brice ; Michael Schuepbach ; Alain Mallet ; Andreas Hartmann ; Jean-Christophe CorvolSource :
- Parkinsonism and Related Disorders [ 1353-8020 ] ; 2015-02-19.
English descriptors
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, COMTHH), intermediate (Val/Met, COMTHL) and low metabolizers (Met/Met, COMTLL). 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%) COMTHH, 26 (65%) COMTHL and 3 (7.5%) COMTLL. 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 (COMTHL+LL BP=1.32 +/- 0.04) than high metabolizers (COMTHH, 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.
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DOI: 10.1016/j.parkreldis.2015.02.009
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Hal:hal-01120290Le document en format XML
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Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1127" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle active="#struct-353778" type="direct"><org type="institution" xml:id="struct-353778" status="VALID"> <orgName>CHU Pitié-Salpêtrière [APHP]</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital, 75013 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.aphp.fr/contenu/hopital-universitaire-pitie-salpetriere-0</ref> </desc></org></tutelle><tutelle name="UMR7225" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Gharrad, Iman" sort="Gharrad, Iman" uniqKey="Gharrad I" first="Iman" last="Gharrad">Iman Gharrad</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-246044" status="VALID"> <idno type="RNSR">200918525B</idno> <orgName>Institut du Cerveau et de la Moëlle Epinière</orgName> <orgName type="acronym">ICM</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital 75651 Paris Cedex 13</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation name="UM75" active="#struct-93591" type="direct"></relation> <relation name="U1127" active="#struct-303623" type="direct"></relation> <relation active="#struct-353778" type="direct"></relation> <relation name="UMR7225" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle name="UM75" active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - 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Bâtiment A/3ème étage - 75006 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.lib.upmc.fr</ref> </desc> <listRelation> <relation name="UM117" active="#struct-93591" type="direct"></relation> <relation name="U1146" active="#struct-303623" type="direct"></relation> <relation name="UMR7371" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle name="UM117" active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1146" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle name="UMR7371" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Martini, Jean Baptiste" sort="Martini, Jean Baptiste" uniqKey="Martini J" first="Jean-Baptiste" last="Martini">Jean-Baptiste Martini</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-245879" status="VALID"> <idno type="RNSR">199712668M</idno> <orgName>Laboratoire d'Imagerie Biomédicale</orgName> <orgName type="acronym">LIB</orgName> <desc> <address> <addrLine>15 rue de l'école de Médecine - Bâtiment A/3ème étage - 75006 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.lib.upmc.fr</ref> </desc> <listRelation> <relation name="UM117" active="#struct-93591" type="direct"></relation> <relation name="U1146" active="#struct-303623" type="direct"></relation> <relation name="UMR7371" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle name="UM117" active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1146" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle name="UMR7371" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Cormier Dequaire, Florence" sort="Cormier Dequaire, Florence" uniqKey="Cormier Dequaire F" first="Florence" last="Cormier-Dequaire">Florence Cormier-Dequaire</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-5370" status="VALID"> <orgName>Département de Neurologie [Paris]</orgName> <desc> <address> <addrLine>47 Bd de l'Hôpital 75651 Paris Cedex 13</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-300068" type="direct"></relation> <relation active="#struct-300636" type="direct"></relation> <relation active="#struct-304503" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300068" type="direct"><org type="institution" xml:id="struct-300068" status="VALID"> <orgName>Assistance publique - 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Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1127" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle active="#struct-353778" type="direct"><org type="institution" xml:id="struct-353778" status="VALID"> <orgName>CHU Pitié-Salpêtrière [APHP]</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital, 75013 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.aphp.fr/contenu/hopital-universitaire-pitie-salpetriere-0</ref> </desc></org></tutelle><tutelle name="UMR7225" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Schuepbach, Michael" sort="Schuepbach, Michael" uniqKey="Schuepbach M" first="Michael" last="Schuepbach">Michael Schuepbach</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-412957" status="INCOMING"> <orgName>Department of neurology</orgName> <desc> <address> <country key="CH"></country> </address> </desc> <listRelation> <relation active="#struct-242559" type="direct"></relation> <relation active="#struct-346409" type="indirect"></relation> </listRelation><tutelles><tutelle active="#struct-242559" type="direct"><org type="laboratory" xml:id="struct-242559" status="VALID"> <orgName>Inselspital</orgName> <desc> <address> <addrLine>Berne</addrLine> <country key="CH"></country> </address> <ref type="url">http://www.insel.ch/fr/</ref> </desc> <listRelation> <relation active="#struct-346409" type="direct"></relation> </listRelation></org></tutelle><tutelle active="#struct-346409" type="indirect"><org type="institution" xml:id="struct-346409" status="INCOMING"> <orgName>Bern University Hospital</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Mallet, Alain" sort="Mallet, Alain" uniqKey="Mallet A" first="Alain" last="Mallet">Alain Mallet</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-412958" status="INCOMING"> <orgName>Laboratory of mathematical and statistical modelisation in biology and medecine</orgName> <desc> <address> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-353778" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-353778" type="direct"><org type="institution" xml:id="struct-353778" status="VALID"> <orgName>CHU Pitié-Salpêtrière [APHP]</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital, 75013 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.aphp.fr/contenu/hopital-universitaire-pitie-salpetriere-0</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-246044" status="VALID"> <idno type="RNSR">200918525B</idno> <orgName>Institut du Cerveau et de la Moëlle Epinière</orgName> <orgName type="acronym">ICM</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital 75651 Paris Cedex 13</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation name="UM75" active="#struct-93591" type="direct"></relation> <relation name="U1127" active="#struct-303623" type="direct"></relation> <relation active="#struct-353778" type="direct"></relation> <relation name="UMR7225" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle name="UM75" active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1127" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle active="#struct-353778" type="direct"><org type="institution" xml:id="struct-353778" status="VALID"> <orgName>CHU Pitié-Salpêtrière [APHP]</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital, 75013 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.aphp.fr/contenu/hopital-universitaire-pitie-salpetriere-0</ref> </desc></org></tutelle><tutelle name="UMR7225" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author><author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><hal:affiliation type="laboratory" xml:id="struct-246044" status="VALID"> <idno type="RNSR">200918525B</idno> <orgName>Institut du Cerveau et de la Moëlle Epinière</orgName> <orgName type="acronym">ICM</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital 75651 Paris Cedex 13</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation name="UM75" active="#struct-93591" type="direct"></relation> <relation name="U1127" active="#struct-303623" type="direct"></relation> <relation active="#struct-353778" type="direct"></relation> <relation name="UMR7225" active="#struct-441569" type="direct"></relation> </listRelation><tutelles><tutelle name="UM75" active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName> <orgName type="acronym">UPMC</orgName> <desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.upmc.fr/</ref> </desc></org></tutelle><tutelle name="U1127" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle active="#struct-353778" type="direct"><org type="institution" xml:id="struct-353778" status="VALID"> <orgName>CHU Pitié-Salpêtrière [APHP]</orgName> <desc> <address> <addrLine>47-83 Boulevard de l'Hôpital, 75013 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.aphp.fr/contenu/hopital-universitaire-pitie-salpetriere-0</ref> </desc></org></tutelle><tutelle name="UMR7225" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation></affiliation></author></analytic><idno type="DOI">10.1016/j.parkreldis.2015.02.009</idno><series><title level="j">Parkinsonism and Related Disorders</title><idno type="ISSN">1353-8020</idno><imprint><date type="datePub">2015-02-19</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>COMT</term><term>Parkinson’s disease</term><term>compensatory mechanism</term><term>dopaminergic denervation</term><term>motor symptoms</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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, COMTHH), intermediate (Val/Met, COMTHL) and low metabolizers (Met/Met, COMTLL). 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%) COMTHH, 26 (65%) COMTHL and 3 (7.5%) COMTLL. 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 (COMTHL+LL BP=1.32 +/- 0.04) than high metabolizers (COMTHH, 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.</div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson’s disease</title> <author role="aut"> <persName> <forename type="first">Julia</forename> <surname>Muellner</surname> </persName> <idno type="halauthorid">1132164</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-412957"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Iman</forename> <surname>Gharrad</surname> </persName> <idno type="halauthorid">1132165</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marie-Odile</forename> <surname>Habert</surname> </persName> <idno type="halauthorid">197185</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Aurélie</forename> <surname>Kas</surname> </persName> <idno type="halauthorid">197187</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jean-Baptiste</forename> <surname>Martini</surname> </persName> <idno type="halauthorid">1132166</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Florence</forename> <surname>Cormier-Dequaire</surname> </persName> <idno type="halauthorid">1132167</idno> <affiliation ref="#struct-5370"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Khadija</forename> <surname>Tahiri</surname> </persName> <idno type="halauthorid">1132168</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marie</forename> <surname>Vidailhet</surname> </persName> <idno type="halauthorid">216232</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Niklaus</forename> <surname>Meier</surname> </persName> <idno type="halauthorid">1132169</idno> <affiliation ref="#struct-412957"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Brice</surname> </persName> <idno type="halauthorid">183596</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Michael</forename> <surname>Schuepbach</surname> </persName> <idno type="halauthorid">1132170</idno> <affiliation ref="#struct-412957"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alain</forename> <surname>Mallet</surname> </persName> <idno type="halauthorid">200837</idno> <affiliation ref="#struct-412958"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Andreas</forename> <surname>Hartmann</surname> </persName> <idno type="halauthorid">362798</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Jean-Christophe</forename> <surname>Corvol</surname> </persName> <email type="md5">baab7640154c232f8fa57ca3c9ed3340</email> <email type="domain">psl.aphp.fr</email> <idno type="halauthorid">1132171</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> <editor role="depositor"> <persName> <forename>Administrateur</forename> <surname>Hal-Upmc</surname> </persName> <email type="md5">5e5f92b30d5a5dc773d73b514d0dc0a4</email> <email type="domain">upmc.fr</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2015-02-25 11:38:43</date> <date type="whenModified">2015-02-26 10:21:36</date> <date type="whenReleased">2015-02-25 11:52:21</date> <date type="whenProduced">2015-02-19</date> <date type="whenEndEmbargoed">2015-02-25</date> <ref type="file" target="http://hal.upmc.fr/hal-01120290/document"> <date notBefore="2015-02-25"></date> </ref> <ref type="file" subtype="author" n="1" target="http://hal.upmc.fr/hal-01120290/file/Muellner_Dopaminergic.pdf"> <date notBefore="2015-02-25"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="163328"> <persName> <forename>Administrateur</forename> <surname>Hal-Upmc</surname> </persName> <email type="md5">5e5f92b30d5a5dc773d73b514d0dc0a4</email> <email type="domain">upmc.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">hal-01120290</idno> <idno type="halUri">http://hal.upmc.fr/hal-01120290</idno> <idno type="halBibtex">muellner:hal-01120290</idno> <idno type="halRefHtml">Parkinsonism and Related Disorders, Elsevier, 2015, in press. <10.1016/j.parkreldis.2015.02.009></idno> <idno type="halRef">Parkinsonism and Related Disorders, Elsevier, 2015, in press. <10.1016/j.parkreldis.2015.02.009></idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="UPMC">Université Pierre et Marie Curie</idno> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> <idno type="stamp" n="APHP" p="INSERM">AP-HP</idno> <idno type="stamp" n="LIB" p="UPMC">Laboratoire d'Imagerie Biomédicale</idno> <idno type="stamp" n="ICM" p="UPMC">Institut du Cerveau et de la Moëlle Epinière</idno> <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson’s disease</title> <author role="aut"> <persName> <forename type="first">Julia</forename> <surname>Muellner</surname> </persName> <idno type="halauthorid">1132164</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-412957"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Iman</forename> <surname>Gharrad</surname> </persName> <idno type="halauthorid">1132165</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marie-Odile</forename> <surname>Habert</surname> </persName> <idno type="halauthorid">197185</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Aurélie</forename> <surname>Kas</surname> </persName> <idno type="halauthorid">197187</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Jean-Baptiste</forename> <surname>Martini</surname> </persName> <idno type="halauthorid">1132166</idno> <affiliation ref="#struct-245879"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Florence</forename> <surname>Cormier-Dequaire</surname> </persName> <idno type="halauthorid">1132167</idno> <affiliation ref="#struct-5370"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Khadija</forename> <surname>Tahiri</surname> </persName> <idno type="halauthorid">1132168</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Marie</forename> <surname>Vidailhet</surname> </persName> <idno type="halauthorid">216232</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Niklaus</forename> <surname>Meier</surname> </persName> <idno type="halauthorid">1132169</idno> <affiliation ref="#struct-412957"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alexis</forename> <surname>Brice</surname> </persName> <idno type="halauthorid">183596</idno> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Michael</forename> <surname>Schuepbach</surname> </persName> <idno type="halauthorid">1132170</idno> <affiliation ref="#struct-412957"></affiliation> <affiliation ref="#struct-246044"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Alain</forename> <surname>Mallet</surname> </persName> <idno type="halauthorid">200837</idno> <affiliation ref="#struct-412958"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Andreas</forename> <surname>Hartmann</surname> </persName> <idno type="halauthorid">362798</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Jean-Christophe</forename> <surname>Corvol</surname> </persName> <email type="md5">baab7640154c232f8fa57ca3c9ed3340</email> <email type="domain">psl.aphp.fr</email> <idno type="halauthorid">1132171</idno> <affiliation ref="#struct-246044"></affiliation> <affiliation ref="#struct-5370"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">17779</idno> <idno type="issn">1353-8020</idno> <title level="j">Parkinsonism and Related Disorders</title> <imprint> <publisher>Elsevier</publisher> <biblScope unit="pp">in press</biblScope> <date type="datePub">2015-02-19</date> <date type="dateEpub">2015-02-19</date> </imprint> </monogr> <idno type="doi">10.1016/j.parkreldis.2015.02.009</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">dopaminergic denervation</term> <term xml:lang="en">Parkinson’s disease</term> <term xml:lang="en">COMT</term> <term xml:lang="en">motor symptoms</term> <term xml:lang="en">compensatory mechanism</term> </keywords> <classCode scheme="halDomain" n="sdv.mhep">Life Sciences [q-bio]/Human health and pathology</classCode> <classCode scheme="halDomain" n="sdv.neu">Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en">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, COMTHH), intermediate (Val/Met, COMTHL) and low metabolizers (Met/Met, COMTLL). 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%) COMTHH, 26 (65%) COMTHL and 3 (7.5%) COMTLL. 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 (COMTHL+LL BP=1.32 +/- 0.04) than high metabolizers (COMTHH, 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.</abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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