Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease
Identifieur interne : 001258 ( Main/Exploration ); précédent : 001257; suivant : 001259Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease
Auteurs : Ikuko Mizuta ; Wataru Satake ; Yuko Nakabayashi ; Chiyomi Ito ; Satoko Suzuki ; Yoshio Momose ; Yoshitaka Nagai ; Akira Oka ; Hidetoshi Inoko ; Jiro Fukae ; Yuko Saito ; Motoji Sawabe ; Shigeo Murayama ; Mitsutoshi Yamamoto ; Nobutaka Hattori ; Miho Murata [Japon] ; Tatsushi Toda [Japon]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2006-04-01.
Abstract
Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case–control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case–control populations, we found that a SNP in α-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0×10−10). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D′>0.9) spanning ∼120 kb. A tight LD group (r2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0×10−9–1.7×10−11). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated with the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.
Url:
DOI: 10.1093/hmg/ddl030
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease</title><author><name sortKey="Mizuta, Ikuko" sort="Mizuta, Ikuko" uniqKey="Mizuta I" first="Ikuko" last="Mizuta">Ikuko Mizuta</name></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name></author><author><name sortKey="Nakabayashi, Yuko" sort="Nakabayashi, Yuko" uniqKey="Nakabayashi Y" first="Yuko" last="Nakabayashi">Yuko Nakabayashi</name></author><author><name sortKey="Ito, Chiyomi" sort="Ito, Chiyomi" uniqKey="Ito C" first="Chiyomi" last="Ito">Chiyomi Ito</name></author><author><name sortKey="Suzuki, Satoko" sort="Suzuki, Satoko" uniqKey="Suzuki S" first="Satoko" last="Suzuki">Satoko Suzuki</name></author><author><name sortKey="Momose, Yoshio" sort="Momose, Yoshio" uniqKey="Momose Y" first="Yoshio" last="Momose">Yoshio Momose</name></author><author><name sortKey="Nagai, Yoshitaka" sort="Nagai, Yoshitaka" uniqKey="Nagai Y" first="Yoshitaka" last="Nagai">Yoshitaka Nagai</name></author><author><name sortKey="Oka, Akira" sort="Oka, Akira" uniqKey="Oka A" first="Akira" last="Oka">Akira Oka</name></author><author><name sortKey="Inoko, Hidetoshi" sort="Inoko, Hidetoshi" uniqKey="Inoko H" first="Hidetoshi" last="Inoko">Hidetoshi Inoko</name></author><author><name sortKey="Fukae, Jiro" sort="Fukae, Jiro" uniqKey="Fukae J" first="Jiro" last="Fukae">Jiro Fukae</name></author><author><name sortKey="Saito, Yuko" sort="Saito, Yuko" uniqKey="Saito Y" first="Yuko" last="Saito">Yuko Saito</name></author><author><name sortKey="Sawabe, Motoji" sort="Sawabe, Motoji" uniqKey="Sawabe M" first="Motoji" last="Sawabe">Motoji Sawabe</name></author><author><name sortKey="Murayama, Shigeo" sort="Murayama, Shigeo" uniqKey="Murayama S" first="Shigeo" last="Murayama">Shigeo Murayama</name></author><author><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name></author><author><name sortKey="Murata, Miho" sort="Murata, Miho" uniqKey="Murata M" first="Miho" last="Murata">Miho Murata</name></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D66103F44B7C0A027672E53C0AC8CA54EFD09265</idno><date when="2006" year="2006">2006</date><idno type="doi">10.1093/hmg/ddl030</idno><idno type="url">https://api.istex.fr/document/D66103F44B7C0A027672E53C0AC8CA54EFD09265/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000590</idno><idno type="wicri:Area/Main/Curation">000514</idno><idno type="wicri:Area/Main/Exploration">001258</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease</title><author><name sortKey="Mizuta, Ikuko" sort="Mizuta, Ikuko" uniqKey="Mizuta I" first="Ikuko" last="Mizuta">Ikuko Mizuta</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nakabayashi, Yuko" sort="Nakabayashi, Yuko" uniqKey="Nakabayashi Y" first="Yuko" last="Nakabayashi">Yuko Nakabayashi</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Ito, Chiyomi" sort="Ito, Chiyomi" uniqKey="Ito C" first="Chiyomi" last="Ito">Chiyomi Ito</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Suzuki, Satoko" sort="Suzuki, Satoko" uniqKey="Suzuki S" first="Satoko" last="Suzuki">Satoko Suzuki</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Momose, Yoshio" sort="Momose, Yoshio" uniqKey="Momose Y" first="Yoshio" last="Momose">Yoshio Momose</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nagai, Yoshitaka" sort="Nagai, Yoshitaka" uniqKey="Nagai Y" first="Yoshitaka" last="Nagai">Yoshitaka Nagai</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Oka, Akira" sort="Oka, Akira" uniqKey="Oka A" first="Akira" last="Oka">Akira Oka</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Inoko, Hidetoshi" sort="Inoko, Hidetoshi" uniqKey="Inoko H" first="Hidetoshi" last="Inoko">Hidetoshi Inoko</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Fukae, Jiro" sort="Fukae, Jiro" uniqKey="Fukae J" first="Jiro" last="Fukae">Jiro Fukae</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Saito, Yuko" sort="Saito, Yuko" uniqKey="Saito Y" first="Yuko" last="Saito">Yuko Saito</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Sawabe, Motoji" sort="Sawabe, Motoji" uniqKey="Sawabe M" first="Motoji" last="Sawabe">Motoji Sawabe</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Murayama, Shigeo" sort="Murayama, Shigeo" uniqKey="Murayama S" first="Shigeo" last="Murayama">Shigeo Murayama</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name><affiliation><wicri:noCountry code="subField">Japan and</wicri:noCountry></affiliation></author><author><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Murata, Miho" sort="Murata, Miho" uniqKey="Murata M" first="Miho" last="Murata">Miho Murata</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Musashi Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8551</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement></placeName></affiliation></author><author><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Japon</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2006-04-01">2006-04-01</date><biblScope unit="volume">15</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1151">1151</biblScope><biblScope unit="page" to="1158">1158</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">D66103F44B7C0A027672E53C0AC8CA54EFD09265</idno><idno type="DOI">10.1093/hmg/ddl030</idno><idno type="href">ddl030</idno><idno type="local">ddl030</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</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), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case–control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case–control populations, we found that a SNP in α-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0×10−10). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D′>0.9) spanning ∼120 kb. A tight LD group (r2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0×10−9–1.7×10−11). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated with the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.</div></front></TEI><affiliations><list><country><li>Japon</li></country><settlement><li>Tokyo</li></settlement></list><tree><noCountry><name sortKey="Fukae, Jiro" sort="Fukae, Jiro" uniqKey="Fukae J" first="Jiro" last="Fukae">Jiro Fukae</name><name sortKey="Hattori, Nobutaka" sort="Hattori, Nobutaka" uniqKey="Hattori N" first="Nobutaka" last="Hattori">Nobutaka Hattori</name><name sortKey="Inoko, Hidetoshi" sort="Inoko, Hidetoshi" uniqKey="Inoko H" first="Hidetoshi" last="Inoko">Hidetoshi Inoko</name><name sortKey="Ito, Chiyomi" sort="Ito, Chiyomi" uniqKey="Ito C" first="Chiyomi" last="Ito">Chiyomi Ito</name><name sortKey="Mizuta, Ikuko" sort="Mizuta, Ikuko" uniqKey="Mizuta I" first="Ikuko" last="Mizuta">Ikuko Mizuta</name><name sortKey="Momose, Yoshio" sort="Momose, Yoshio" uniqKey="Momose Y" first="Yoshio" last="Momose">Yoshio Momose</name><name sortKey="Murayama, Shigeo" sort="Murayama, Shigeo" uniqKey="Murayama S" first="Shigeo" last="Murayama">Shigeo Murayama</name><name sortKey="Nagai, Yoshitaka" sort="Nagai, Yoshitaka" uniqKey="Nagai Y" first="Yoshitaka" last="Nagai">Yoshitaka Nagai</name><name sortKey="Nakabayashi, Yuko" sort="Nakabayashi, Yuko" uniqKey="Nakabayashi Y" first="Yuko" last="Nakabayashi">Yuko Nakabayashi</name><name sortKey="Oka, Akira" sort="Oka, Akira" uniqKey="Oka A" first="Akira" last="Oka">Akira Oka</name><name sortKey="Saito, Yuko" sort="Saito, Yuko" uniqKey="Saito Y" first="Yuko" last="Saito">Yuko Saito</name><name sortKey="Satake, Wataru" sort="Satake, Wataru" uniqKey="Satake W" first="Wataru" last="Satake">Wataru Satake</name><name sortKey="Sawabe, Motoji" sort="Sawabe, Motoji" uniqKey="Sawabe M" first="Motoji" last="Sawabe">Motoji Sawabe</name><name sortKey="Suzuki, Satoko" sort="Suzuki, Satoko" uniqKey="Suzuki S" first="Satoko" last="Suzuki">Satoko Suzuki</name><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name></noCountry><country name="Japon"><noRegion><name sortKey="Murata, Miho" sort="Murata, Miho" uniqKey="Murata M" first="Miho" last="Murata">Miho Murata</name></noRegion><name sortKey="Toda, Tatsushi" sort="Toda, Tatsushi" uniqKey="Toda T" first="Tatsushi" last="Toda">Tatsushi Toda</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001258 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001258 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:D66103F44B7C0A027672E53C0AC8CA54EFD09265
|texte= Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease
}}
| This area was generated with Dilib version V0.6.23. |  |