Multiple regions of α‐synuclein are associated with Parkinson's disease
Identifieur interne : 001463 ( Main/Exploration ); précédent : 001462; suivant : 001464Multiple regions of α‐synuclein are associated with Parkinson's disease
Auteurs : Jakob C. Mueller [Allemagne] ; Julia Fuchs [Allemagne] ; Anne Hofer [Allemagne] ; Alexander Zimprich [Autriche] ; Peter Lichtner [Allemagne] ; Thomas Illig [Allemagne] ; Daniela Berg [Allemagne] ; Ullrich Wüllner [Allemagne] ; Thomas Meitinger [Allemagne] ; Thomas Gasser [Allemagne]Source :
- Annals of Neurology [ 0364-5134 ] ; 2005-04.
Abstract
α‐Synuclein is considered to play an important role in the pathogenesis of both the rare familial and the common sporadic forms of Parkinson's disease. Previous reports primarily have tested the association of α‐synuclein promoter polymorphisms with idiopathic Parkinson's disease, but results are controversial. We first characterized the linkage disequilibrium structure of the α‐synuclein gene region with a dense set of 56 genetic markers and subsequently performed two independent case–control association analyses using tagging markers. We could distinguish two large linkage disequilibrium blocks spanning the α‐synuclein gene. Several markers within the 3′‐block around exons 5 and 6 showed strong association with Parkinson's disease (p = 0.00009). Effects of the associated variants might be mediated by regulatory elements in this highly conserved region or by a frequency shift in a previously described splice variant lacking exon 5. A direct association with promoter polymorphisms could not be replicated in our sample set. A second set of markers in the 5′‐block of the gene were also significantly associated with Parkinson's disease, when young patients and female subjects were analyzed separately. These findings indicate locus heterogeneity for the pathogenesis of Parkinson's disease in different genetic or physiological environments, related to sex and age. Ann Neurol 2005;57:535–541
Url:
DOI: 10.1002/ana.20438
Affiliations:
- Allemagne, Autriche
- Bade-Wurtemberg, District de Cologne, District de Tübingen, Rhénanie-du-Nord-Westphalie, Vienne (Autriche)
- Bonn, Tübingen, Vienne (Autriche)
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type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2005-04">2005-04</date><biblScope unit="volume">57</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="535">535</biblScope><biblScope unit="page" to="541">541</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">B5631BC42A7F6873BB6F2CCF2D55C96B83E1C69E</idno><idno type="DOI">10.1002/ana.20438</idno><idno type="ArticleID">ANA20438</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">α‐Synuclein is considered to play an important role in the pathogenesis of both the rare familial and the common sporadic forms of Parkinson's disease. Previous reports primarily have tested the association of α‐synuclein promoter polymorphisms with idiopathic Parkinson's disease, but results are controversial. We first characterized the linkage disequilibrium structure of the α‐synuclein gene region with a dense set of 56 genetic markers and subsequently performed two independent case–control association analyses using tagging markers. We could distinguish two large linkage disequilibrium blocks spanning the α‐synuclein gene. Several markers within the 3′‐block around exons 5 and 6 showed strong association with Parkinson's disease (p = 0.00009). Effects of the associated variants might be mediated by regulatory elements in this highly conserved region or by a frequency shift in a previously described splice variant lacking exon 5. A direct association with promoter polymorphisms could not be replicated in our sample set. A second set of markers in the 5′‐block of the gene were also significantly associated with Parkinson's disease, when young patients and female subjects were analyzed separately. These findings indicate locus heterogeneity for the pathogenesis of Parkinson's disease in different genetic or physiological environments, related to sex and age. Ann Neurol 2005;57:535–541</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Autriche</li></country><region><li>Bade-Wurtemberg</li><li>District de Cologne</li><li>District de Tübingen</li><li>Rhénanie-du-Nord-Westphalie</li><li>Vienne (Autriche)</li></region><settlement><li>Bonn</li><li>Tübingen</li><li>Vienne (Autriche)</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Mueller, Jakob C" sort="Mueller, Jakob C" uniqKey="Mueller J" first="Jakob C." last="Mueller">Jakob C. Mueller</name></noRegion><name sortKey="Berg, Daniela" sort="Berg, Daniela" uniqKey="Berg D" first="Daniela" last="Berg">Daniela Berg</name><name sortKey="Fuchs, Julia" sort="Fuchs, Julia" uniqKey="Fuchs J" first="Julia" last="Fuchs">Julia Fuchs</name><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name><name sortKey="Hofer, Anne" sort="Hofer, Anne" uniqKey="Hofer A" first="Anne" last="Hofer">Anne Hofer</name><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><name sortKey="Wullner, Ullrich" sort="Wullner, Ullrich" uniqKey="Wullner U" first="Ullrich" last="Wüllner">Ullrich Wüllner</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Zimprich, Alexander" sort="Zimprich, Alexander" uniqKey="Zimprich A" first="Alexander" last="Zimprich">Alexander Zimprich</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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