Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype
Identifieur interne : 000C30 ( Main/Corpus ); précédent : 000C29; suivant : 000C31Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype
Auteurs : Rejko Krüger ; Ana Maria Menezes Vieira-Saecker ; Wilfried Kuhn ; Daniela Berg ; Thomas Müller ; Natalia Kühnl ; Gerd A. Fuchs ; Alexander Storch ; Marcel Hungs ; Dirk Woitalla ; Horst Przuntek ; Jörg T. Epplen ; Ludger Schöls ; Olaf RiessSource :
- Annals of Neurology [ 0364-5134 ] ; 1999-05.
Abstract
Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617
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DOI: 10.1002/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X
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Fuchs</name><affiliation><mods:affiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</mods:affiliation></affiliation></author><author><name sortKey="Storch, Alexander" sort="Storch, Alexander" uniqKey="Storch A" first="Alexander" last="Storch">Alexander Storch</name><affiliation><mods:affiliation>Department of Neurology, University of Ulm, Ulm, Germany</mods:affiliation></affiliation></author><author><name sortKey="Hungs, Marcel" sort="Hungs, Marcel" uniqKey="Hungs M" first="Marcel" last="Hungs">Marcel Hungs</name><affiliation><mods:affiliation>Department of Neurology, RWTH Aachen, Aachen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Woitalla, Dirk" sort="Woitalla, Dirk" uniqKey="Woitalla D" first="Dirk" last="Woitalla">Dirk Woitalla</name><affiliation><mods:affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Przuntek, Horst" sort="Przuntek, Horst" uniqKey="Przuntek H" first="Horst" last="Przuntek">Horst Przuntek</name><affiliation><mods:affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Epplen, Jorg T" sort="Epplen, Jorg T" uniqKey="Epplen J" first="Jörg T." last="Epplen">Jörg T. Epplen</name><affiliation><mods:affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Schols, Ludger" sort="Schols, Ludger" uniqKey="Schols L" first="Ludger" last="Schöls">Ludger Schöls</name><affiliation><mods:affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</mods:affiliation></affiliation></author><author><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name><affiliation><mods:affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1999-05">1999-05</date><biblScope unit="volume">45</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="611">611</biblScope><biblScope unit="page" to="617">617</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">69DBA508DB0E45234029CA53EE566CDAAE0D4BB0</idno><idno type="DOI">10.1002/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X</idno><idno type="ArticleID">ANA9</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Rejko Krüger MD</name><affiliations><json:string>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</json:string><json:string>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Ana Maria Menezes Vieira‐Saecker</name><affiliations><json:string>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Wilfried Kuhn MD</name><affiliations><json:string>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Daniela Berg MD</name><affiliations><json:string>Department of Neurology, University of Würzburg, Würzburg, Germany</json:string></affiliations></json:item><json:item><name>Thomas Müller MD</name><affiliations><json:string>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Natalia Kühnl MD</name><affiliations><json:string>Parkinson‐Klinik Wolfach, Wolfach, Germany</json:string></affiliations></json:item><json:item><name>Gerd A. Fuchs MD</name><affiliations><json:string>Parkinson‐Klinik Wolfach, Wolfach, Germany</json:string></affiliations></json:item><json:item><name>Alexander Storch MD</name><affiliations><json:string>Department of Neurology, University of Ulm, Ulm, Germany</json:string></affiliations></json:item><json:item><name>Marcel Hungs MD</name><affiliations><json:string>Department of Neurology, RWTH Aachen, Aachen, Germany</json:string></affiliations></json:item><json:item><name>Dirk Woitalla MD</name><affiliations><json:string>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Horst Przuntek MD</name><affiliations><json:string>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Jörg T. Epplen MD</name><affiliations><json:string>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Ludger Schöls MD</name><affiliations><json:string>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Olaf Riess MD</name><affiliations><json:string>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</json:string></affiliations></json:item></author><articleId><json:string>ANA9</json:string></articleId><language><json:string>eng</json:string></language><abstract>Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, >50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617</abstract><qualityIndicators><score>7.558</score><pdfVersion>1.2</pdfVersion><pdfPageSize>605 x 786 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1789</abstractCharCount><pdfWordCount>4558</pdfWordCount><pdfCharCount>27623</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>265</abstractWordCount></qualityIndicators><title>Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype</title><genre><json:string>article</json:string></genre><host><volume>45</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>7</total><last>617</last><first>611</first></pages><issn><json:string>0364-5134</json:string></issn><issue>5</issue><subject><json:item><value>Original 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Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Ana Maria</forename><surname>Menezes Vieira‐Saecker</surname></persName><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Wilfried</forename><surname>Kuhn</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Daniela</forename><surname>Berg</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Würzburg, Würzburg, Germany</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Müller</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Natalia</forename><surname>Kühnl</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</affiliation></author><author><persName><forename type="first">Gerd A.</forename><surname>Fuchs</surname></persName><roleName type="degree">MD</roleName><affiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</affiliation></author><author><persName><forename type="first">Alexander</forename><surname>Storch</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation></author><author><persName><forename type="first">Marcel</forename><surname>Hungs</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, RWTH Aachen, Aachen, Germany</affiliation></author><author><persName><forename type="first">Dirk</forename><surname>Woitalla</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Horst</forename><surname>Przuntek</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Jörg T.</forename><surname>Epplen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Ludger</forename><surname>Schöls</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Olaf</forename><surname>Riess</surname></persName><roleName type="degree">MD</roleName><note type="correspondence"><p>Correspondence: Department of Medical Genetics, Children's Hospital, University Rostock, Rembrandt Str. 16/17, 18055 Rostock, Germany</p></note><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="sub">Official Journal of the American Neurological Association and the Child Neurology Society</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1999-05"></date><biblScope unit="volume">45</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="611">611</biblScope><biblScope unit="page" to="617">617</biblScope></imprint></monogr><idno type="istex">69DBA508DB0E45234029CA53EE566CDAAE0D4BB0</idno><idno type="DOI">10.1002/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X</idno><idno type="ArticleID">ANA9</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. 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York</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="subtitle">Official Journal of the American Neurological Association and the Child Neurology Society</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="50"><doi origin="wiley" registered="yes">10.1002/1531-8249(199905)45:5<>1.0.CO;2-7</doi><numberingGroup><numbering type="journalVolume" number="45">45</numbering><numbering type="journalIssue">5</numbering></numberingGroup><coverDate startDate="1999-05">May 1999</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="9" status="forIssue"><doi origin="wiley" registered="yes">10.1002/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X</doi><idGroup><id type="unit" value="ANA9"></id></idGroup><countGroup><count type="pageTotal" number="7"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 1999 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="1998-09-09"></event><event type="manuscriptRevised" date="1999-01-12"></event><event type="manuscriptAccepted" date="1999-01-12"></event><event type="firstOnline" date="2001-06-01"></event><event type="publishedOnlineFinalForm" date="2001-06-01"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.1 mode:FullText source:HeaderRef result:HeaderRef" date="2010-02-23"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event 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PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Rejko</givenNames><familyName>Krüger</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Ana Maria</givenNames><familyName>Menezes Vieira‐Saecker</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Wilfried</givenNames><familyName>Kuhn</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Daniela</givenNames><familyName>Berg</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Thomas</givenNames><familyName>Müller</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Natalia</givenNames><familyName>Kühnl</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Gerd A.</givenNames><familyName>Fuchs</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Alexander</givenNames><familyName>Storch</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Marcel</givenNames><familyName>Hungs</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Dirk</givenNames><familyName>Woitalla</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Horst</givenNames><familyName>Przuntek</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Jörg T.</givenNames><familyName>Epplen</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Ludger</givenNames><familyName>Schöls</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Olaf</givenNames><familyName>Riess</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DE" type="organization"><unparsedAffiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="DE" type="organization"><unparsedAffiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, University of Würzburg, Würzburg, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, University of Ulm, Ulm, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neurology, RWTH Aachen, Aachen, Germany</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Increased Susceptibility to Sporadic PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Increased susceptibility to sporadic Parkinson's disease by a certain combined α‐synuclein/apolipoprotein E genotype</title></titleInfo><name type="personal"><namePart type="given">Rejko</namePart><namePart type="family">Krüger</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ana Maria</namePart><namePart type="family">Menezes Vieira‐Saecker</namePart><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wilfried</namePart><namePart type="family">Kuhn</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Daniela</namePart><namePart type="family">Berg</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Würzburg, Würzburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Müller</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Natalia</namePart><namePart type="family">Kühnl</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gerd A.</namePart><namePart type="family">Fuchs</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Parkinson‐Klinik Wolfach, Wolfach, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexander</namePart><namePart type="family">Storch</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Ulm, Ulm, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marcel</namePart><namePart type="family">Hungs</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, RWTH Aachen, Aachen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dirk</namePart><namePart type="family">Woitalla</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Horst</namePart><namePart type="family">Przuntek</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jörg T.</namePart><namePart type="family">Epplen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ludger</namePart><namePart type="family">Schöls</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olaf</namePart><namePart type="family">Riess</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Molecular Human Genetics, Ruhr‐University of Bochum, Bochum, Germany</affiliation><description>Correspondence: Department of Medical Genetics, Children's Hospital, University Rostock, Rembrandt Str. 16/17, 18055 Rostock, Germany</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">1999-05</dateIssued><dateCaptured encoding="w3cdtf">1998-09-09</dateCaptured><dateValid encoding="w3cdtf">1999-01-12</dateValid><copyrightDate encoding="w3cdtf">1999</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">5</extent><extent unit="references">38</extent><extent unit="words">5450</extent></physicalDescription><abstract lang="en">Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title><subTitle>Official Journal of the American Neurological Association and the Child Neurology Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>45</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>611</start><end>617</end><total>7</total></extent></part></relatedItem><identifier type="istex">69DBA508DB0E45234029CA53EE566CDAAE0D4BB0</identifier><identifier type="DOI">10.1002/1531-8249(199905)45:5<611::AID-ANA9>3.0.CO;2-X</identifier><identifier type="ArticleID">ANA9</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 1999 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>John Wiley & Sons, Inc.</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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