BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease
Identifieur interne : 000F10 ( Main/Corpus ); précédent : 000F09; suivant : 000F11BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease
Auteurs : F. R. Guerini ; E. Beghi ; G. Riboldazzi ; R. Zangaglia ; C. Pianezzola ; G. Bono ; C. Casali ; C. Di Lorenzo ; C. Agliardi ; G. Nappi ; M. Clerici ; E. MartignoniSource :
- European Journal of Neurology [ 1351-5101 ] ; 2009-11.
English descriptors
Abstract
Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment. Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.
Url:
DOI: 10.1111/j.1468-1331.2009.02706.x
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R." last="Guerini">F. R. Guerini</name><affiliation><mods:affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</mods:affiliation></affiliation></author><author><name sortKey="Beghi, E" sort="Beghi, E" uniqKey="Beghi E" first="E." last="Beghi">E. Beghi</name><affiliation><mods:affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</mods:affiliation></affiliation><affiliation><mods:affiliation>Laboratory of Neurological Disorders, Mario Negri Institute, Milan</mods:affiliation></affiliation></author><author><name sortKey="Riboldazzi, G" sort="Riboldazzi, G" uniqKey="Riboldazzi G" first="G." last="Riboldazzi">G. Riboldazzi</name><affiliation><mods:affiliation>Center for Parkinson’s Disease and Movement Disorders, Ospedale di Circolo e Fondazioni Macchi, Varese</mods:affiliation></affiliation></author><author><name sortKey="Zangaglia, R" sort="Zangaglia, R" uniqKey="Zangaglia R" first="R." last="Zangaglia">R. Zangaglia</name><affiliation><mods:affiliation>Parkinson’s disease and Movement Disorders Unit, IRCCS Neurological Institute “C. Mondino”, Pavia</mods:affiliation></affiliation></author><author><name sortKey="Pianezzola, C" sort="Pianezzola, C" uniqKey="Pianezzola C" first="C." last="Pianezzola">C. Pianezzola</name><affiliation><mods:affiliation>Department of Neurology, University of Insubria, Varese</mods:affiliation></affiliation></author><author><name sortKey="Bono, G" sort="Bono, G" uniqKey="Bono G" first="G." last="Bono">G. Bono</name><affiliation><mods:affiliation>Department of Neurology, University of Insubria, Varese</mods:affiliation></affiliation></author><author><name sortKey="Casali, C" sort="Casali, C" uniqKey="Casali C" first="C." last="Casali">C. Casali</name><affiliation><mods:affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</mods:affiliation></affiliation></author><author><name sortKey="Di Lorenzo, C" sort="Di Lorenzo, C" uniqKey="Di Lorenzo C" first="C." last="Di Lorenzo">C. Di Lorenzo</name><affiliation><mods:affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</mods:affiliation></affiliation></author><author><name sortKey="Agliardi, C" sort="Agliardi, C" uniqKey="Agliardi C" first="C." last="Agliardi">C. Agliardi</name><affiliation><mods:affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</mods:affiliation></affiliation></author><author><name sortKey="Nappi, G" sort="Nappi, G" uniqKey="Nappi G" first="G." last="Nappi">G. Nappi</name><affiliation><mods:affiliation>Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome</mods:affiliation></affiliation></author><author><name sortKey="Clerici, M" sort="Clerici, M" uniqKey="Clerici M" first="M." last="Clerici">M. Clerici</name><affiliation><mods:affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Biomedical Sciences and Technology, University of Milan, Milan</mods:affiliation></affiliation></author><author><name sortKey="Martignoni, E" sort="Martignoni, E" uniqKey="Martignoni E" first="E." last="Martignoni">E. Martignoni</name><affiliation><mods:affiliation>Interdepartmental Research Center for Parkinson’s disease, IRCCS Neurological Institute “C. Mondino”, Pavia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara</mods:affiliation></affiliation><affiliation><mods:affiliation>Unit of Neurorehabilitation and Movement Disorders, IRCCS Maugeri, Scientific Institute of Veruno, Novara, Italy</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neurology</title><idno type="ISSN">1351-5101</idno><idno type="eISSN">1468-1331</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-11">2009-11</date><biblScope unit="volume">16</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1240">1240</biblScope><biblScope unit="page" to="1245">1245</biblScope></imprint><idno type="ISSN">1351-5101</idno></series><idno type="istex">3A8EF4C4150EB8E31B07FFD9927254575D144DD0</idno><idno type="DOI">10.1111/j.1468-1331.2009.02706.x</idno><idno type="ArticleID">ENE2706</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1351-5101</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Brain Derived Neurotrophic Factor</term><term>Mini Mental State Examination</term><term>Parkinson's disease</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment. Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>F. R. Guerini</name><affiliations><json:string>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</json:string></affiliations></json:item><json:item><name>E. Beghi</name><affiliations><json:string>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</json:string><json:string>Laboratory of Neurological Disorders, Mario Negri Institute, Milan</json:string></affiliations></json:item><json:item><name>G. Riboldazzi</name><affiliations><json:string>Center for Parkinson’s Disease and Movement Disorders, Ospedale di Circolo e Fondazioni Macchi, Varese</json:string></affiliations></json:item><json:item><name>R. Zangaglia</name><affiliations><json:string>Parkinson’s disease and Movement Disorders Unit, IRCCS Neurological Institute “C. Mondino”, Pavia</json:string></affiliations></json:item><json:item><name>C. Pianezzola</name><affiliations><json:string>Department of Neurology, University of Insubria, Varese</json:string></affiliations></json:item><json:item><name>G. Bono</name><affiliations><json:string>Department of Neurology, University of Insubria, Varese</json:string></affiliations></json:item><json:item><name>C. Casali</name><affiliations><json:string>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</json:string></affiliations></json:item><json:item><name>C. Di Lorenzo</name><affiliations><json:string>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</json:string></affiliations></json:item><json:item><name>C. Agliardi</name><affiliations><json:string>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</json:string></affiliations></json:item><json:item><name>G. Nappi</name><affiliations><json:string>Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome</json:string></affiliations></json:item><json:item><name>M. Clerici</name><affiliations><json:string>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</json:string><json:string>Department of Biomedical Sciences and Technology, University of Milan, Milan</json:string></affiliations></json:item><json:item><name>E. Martignoni</name><affiliations><json:string>Interdepartmental Research Center for Parkinson’s disease, IRCCS Neurological Institute “C. Mondino”, Pavia</json:string><json:string>Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara</json:string><json:string>Unit of Neurorehabilitation and Movement Disorders, IRCCS Maugeri, Scientific Institute of Veruno, Novara, Italy</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Brain Derived Neurotrophic Factor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Mini Mental State Examination</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item></subject><articleId><json:string>ENE2706</json:string></articleId><language><json:string>eng</json:string></language><abstract>Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P > 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment. Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.</abstract><qualityIndicators><score>6.394</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>3</keywordCount><abstractCharCount>1613</abstractCharCount><pdfWordCount>3670</pdfWordCount><pdfCharCount>23294</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>227</abstractWordCount></qualityIndicators><title>BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title><genre><json:string>article</json:string></genre><host><volume>16</volume><publisherId><json:string>ENE</json:string></publisherId><pages><total>6</total><last>1245</last><first>1240</first></pages><issn><json:string>1351-5101</json:string></issn><issue>11</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1468-1331</json:string></eissn><title>European Journal of Neurology</title><doi><json:string>10.1111/(ISSN)1468-1331</json:string></doi></host><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1111/j.1468-1331.2009.02706.x</json:string></doi><id>3A8EF4C4150EB8E31B07FFD9927254575D144DD0</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/3A8EF4C4150EB8E31B07FFD9927254575D144DD0/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/3A8EF4C4150EB8E31B07FFD9927254575D144DD0/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/3A8EF4C4150EB8E31B07FFD9927254575D144DD0/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><availability><p>WILEY</p></availability><date>2009</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title><author><persName><forename type="first">F. R.</forename><surname>Guerini</surname></persName><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation></author><author><persName><forename type="first">E.</forename><surname>Beghi</surname></persName><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><affiliation>Laboratory of Neurological Disorders, Mario Negri Institute, Milan</affiliation></author><author><persName><forename type="first">G.</forename><surname>Riboldazzi</surname></persName><affiliation>Center for Parkinson’s Disease and Movement Disorders, Ospedale di Circolo e Fondazioni Macchi, Varese</affiliation></author><author><persName><forename type="first">R.</forename><surname>Zangaglia</surname></persName><affiliation>Parkinson’s disease and Movement Disorders Unit, IRCCS Neurological Institute “C. Mondino”, Pavia</affiliation></author><author><persName><forename type="first">C.</forename><surname>Pianezzola</surname></persName><affiliation>Department of Neurology, University of Insubria, Varese</affiliation></author><author><persName><forename type="first">G.</forename><surname>Bono</surname></persName><affiliation>Department of Neurology, University of Insubria, Varese</affiliation></author><author><persName><forename type="first">C.</forename><surname>Casali</surname></persName><affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</affiliation></author><author><persName><forename type="first">C.</forename><surname>Di Lorenzo</surname></persName><affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</affiliation></author><author><persName><forename type="first">C.</forename><surname>Agliardi</surname></persName><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation></author><author><persName><forename type="first">G.</forename><surname>Nappi</surname></persName><affiliation>Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome</affiliation></author><author><persName><forename type="first">M.</forename><surname>Clerici</surname></persName><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><affiliation>Department of Biomedical Sciences and Technology, University of Milan, Milan</affiliation></author><author><persName><forename type="first">E.</forename><surname>Martignoni</surname></persName><affiliation>Interdepartmental Research Center for Parkinson’s disease, IRCCS Neurological Institute “C. Mondino”, Pavia</affiliation><affiliation>Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara</affiliation><affiliation>Unit of Neurorehabilitation and Movement Disorders, IRCCS Maugeri, Scientific Institute of Veruno, Novara, Italy</affiliation></author></analytic><monogr><title level="j">European Journal of Neurology</title><idno type="pISSN">1351-5101</idno><idno type="eISSN">1468-1331</idno><idno type="DOI">10.1111/(ISSN)1468-1331</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-11"></date><biblScope unit="volume">16</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1240">1240</biblScope><biblScope unit="page" to="1245">1245</biblScope></imprint></monogr><idno type="istex">3A8EF4C4150EB8E31B07FFD9927254575D144DD0</idno><idno type="DOI">10.1111/j.1468-1331.2009.02706.x</idno><idno type="ArticleID">ENE2706</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment. Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Brain Derived Neurotrophic Factor</term></item><item><term>Mini Mental State Examination</term></item><item><term>Parkinson's disease</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-11">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/3A8EF4C4150EB8E31B07FFD9927254575D144DD0/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1468-1331</doi><issn type="print">1351-5101</issn><issn type="electronic">1468-1331</issn><idGroup><id type="product" value="ENE"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="EUROPEAN JOURNAL OF NEUROLOGY">European Journal of Neurology</title></titleGroup></publicationMeta><publicationMeta level="part" position="11011"><doi origin="wiley">10.1111/ene.2009.16.issue-11</doi><numberingGroup><numbering type="journalVolume" number="16">16</numbering><numbering type="journalIssue" number="11">11</numbering></numberingGroup><coverDate startDate="2009-11">November 2009</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="14" status="forIssue"><doi origin="wiley">10.1111/j.1468-1331.2009.02706.x</doi><idGroup><id type="unit" value="ENE2706"></id></idGroup><countGroup><count type="pageTotal" number="6"></count></countGroup><titleGroup><title type="tocHeading1">Original Articles</title></titleGroup><copyright>© 2009 The Author(s). Journal compilation © 2009 EFNS</copyright><eventGroup><event type="firstOnline" date="2009-06-15"></event><event type="publishedOnlineFinalForm" date="2009-10-15"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:FullText result:FullText" date="2010-03-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-24"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="1240">1240</numbering><numbering type="pageLast" number="1245">1245</numbering></numberingGroup><correspondenceTo>Franca Rosa Guerini, Laboratory of Molecular Medicine and Biotechnology, IRCCS S. Maria Nascente, Don Gnocchi Foundation, Via Capecelatro 66, 20148 Milan, Italy (tel.: +39 02 40308376; fax: +39 02 40308438; e‐mail: <email>fguerini@dongnocchi.it</email>).</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ENE.ENE2706.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 30 January 2009 Accepted 29 April 2009</unparsedEditorialHistory><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="3"></count></countGroup><titleGroup><title type="main">BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title><title type="shortAuthors">F. R. Guerini <i>et al.</i></title><title type="short">Cognitive impairments in Parkinson’s disease</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>F. R.</givenNames><familyName>Guerini</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1 #a2"><personName><givenNames>E.</givenNames><familyName>Beghi</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a3"><personName><givenNames>G.</givenNames><familyName>Riboldazzi</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a4"><personName><givenNames>R.</givenNames><familyName>Zangaglia</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a5"><personName><givenNames>C.</givenNames><familyName>Pianezzola</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a5"><personName><givenNames>G.</givenNames><familyName>Bono</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a6"><personName><givenNames>C.</givenNames><familyName>Casali</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a6"><personName><givenNames>C.</givenNames><familyName>Di Lorenzo</familyName></personName></creator><creator creatorRole="author" xml:id="cr9" affiliationRef="#a1"><personName><givenNames>C.</givenNames><familyName>Agliardi</familyName></personName></creator><creator creatorRole="author" xml:id="cr10" affiliationRef="#a7"><personName><givenNames>G.</givenNames><familyName>Nappi</familyName></personName></creator><creator creatorRole="author" xml:id="cr11" affiliationRef="#a1 #a8"><personName><givenNames>M.</givenNames><familyName>Clerici</familyName></personName></creator><creator creatorRole="author" xml:id="cr12" affiliationRef="#a9 #a10 #a11"><personName><givenNames>E.</givenNames><familyName>Martignoni</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</unparsedAffiliation></affiliation><affiliation xml:id="a2"><unparsedAffiliation>Laboratory of Neurological Disorders, Mario Negri Institute, Milan</unparsedAffiliation></affiliation><affiliation xml:id="a3"><unparsedAffiliation>Center for Parkinson’s Disease and Movement Disorders, Ospedale di Circolo e Fondazioni Macchi, Varese</unparsedAffiliation></affiliation><affiliation xml:id="a4"><unparsedAffiliation>Parkinson’s disease and Movement Disorders Unit, IRCCS Neurological Institute “C. Mondino”, Pavia</unparsedAffiliation></affiliation><affiliation xml:id="a5"><unparsedAffiliation>Department of Neurology, University of Insubria, Varese</unparsedAffiliation></affiliation><affiliation xml:id="a6"><unparsedAffiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</unparsedAffiliation></affiliation><affiliation xml:id="a7"><unparsedAffiliation>Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome</unparsedAffiliation></affiliation><affiliation xml:id="a8"><unparsedAffiliation>Department of Biomedical Sciences and Technology, University of Milan, Milan</unparsedAffiliation></affiliation><affiliation xml:id="a9"><unparsedAffiliation>Interdepartmental Research Center for Parkinson’s disease, IRCCS Neurological Institute “C. Mondino”, Pavia</unparsedAffiliation></affiliation><affiliation xml:id="a10"><unparsedAffiliation>Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara</unparsedAffiliation></affiliation><affiliation xml:id="a11" countryCode="IT"><unparsedAffiliation>Unit of Neurorehabilitation and Movement Disorders, IRCCS Maugeri, Scientific Institute of Veruno, Novara, Italy</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Brain Derived Neurotrophic Factor</keyword><keyword xml:id="k2">Mini Mental State Examination</keyword><keyword xml:id="k3">Parkinson's disease</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>Background and purpose: </b> A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients.</p><p><b>Methods: </b> The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score.</p><p><b>Results: </b> Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (<i>P</i> < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment.</p><p><b>Conclusions: </b> The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title></titleInfo><titleInfo type="abbreviated"><title>Cognitive impairments in Parkinson’s disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>BDNF Val66Met polymorphism is associated with cognitive impairment in Italian patients with Parkinson’s disease</title></titleInfo><name type="personal"><namePart type="given">F. R.</namePart><namePart type="family">Guerini</namePart><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Beghi</namePart><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><affiliation>Laboratory of Neurological Disorders, Mario Negri Institute, Milan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Riboldazzi</namePart><affiliation>Center for Parkinson’s Disease and Movement Disorders, Ospedale di Circolo e Fondazioni Macchi, Varese</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Zangaglia</namePart><affiliation>Parkinson’s disease and Movement Disorders Unit, IRCCS Neurological Institute “C. Mondino”, Pavia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Pianezzola</namePart><affiliation>Department of Neurology, University of Insubria, Varese</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Bono</namePart><affiliation>Department of Neurology, University of Insubria, Varese</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Casali</namePart><affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Di Lorenzo</namePart><affiliation>Laboratory of Molecolar Neurogenetics, IRCCS Neurological Institute “C. Mondino”, Rome</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C.</namePart><namePart type="family">Agliardi</namePart><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Nappi</namePart><affiliation>Department of Neurology and Otorhinolaryngology, University of Rome “La Sapienza”, Rome</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Clerici</namePart><affiliation>Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi Foundation IRCCS, Milan</affiliation><affiliation>Department of Biomedical Sciences and Technology, University of Milan, Milan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Martignoni</namePart><affiliation>Interdepartmental Research Center for Parkinson’s disease, IRCCS Neurological Institute “C. Mondino”, Pavia</affiliation><affiliation>Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara</affiliation><affiliation>Unit of Neurorehabilitation and Movement Disorders, IRCCS Maugeri, Scientific Institute of Veruno, Novara, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2009-11</dateIssued><edition>Received 30 January 2009 Accepted 29 April 2009</edition><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">3</extent></physicalDescription><abstract lang="en">Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients. Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score. Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment. Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.</abstract><subject lang="en"><genre>Keywords</genre><topic>Brain Derived Neurotrophic Factor</topic><topic>Mini Mental State Examination</topic><topic>Parkinson's disease</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Neurology</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">1351-5101</identifier><identifier type="eISSN">1468-1331</identifier><identifier type="DOI">10.1111/(ISSN)1468-1331</identifier><identifier type="PublisherID">ENE</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>16</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>1240</start><end>1245</end><total>6</total></extent></part></relatedItem><identifier type="istex">3A8EF4C4150EB8E31B07FFD9927254575D144DD0</identifier><identifier type="DOI">10.1111/j.1468-1331.2009.02706.x</identifier><identifier type="ArticleID">ENE2706</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2009 The Author(s). 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