Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study
Identifieur interne : 000A00 ( Main/Corpus ); précédent : 000999; suivant : 000A01Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study
Auteurs : Eng-King Tan ; Rong Peng ; Yik-Ying Teo ; Louis C. Tan ; Dario Angeles ; Patrick Ho ; Meng-Ling Chen ; Chin-Hsien Lin ; Xue-Ye Mao ; Xue-Li Chang ; Kumar M. Prakash ; Jian-Jun Liu ; Wing-Lok Au ; Wei-Dong Le ; Joseph Jankovic ; Jean-Marc Burgunder ; Yi Zhao ; Ruey-Meei WuSource :
- Human Mutation [ 1059-7794 ] ; 2010-05.
English descriptors
- KwdEn :
Abstract
We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/humu.21225
Links to Exploration step
ISTEX:3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FFLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title><author><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Clinical Research, Singapore General Hospital, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Duke–NUS Graduate Medical School, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Peng, Rong" sort="Peng, Rong" uniqKey="Peng R" first="Rong" last="Peng">Rong Peng</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Teo, Yik Ing" sort="Teo, Yik Ing" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><mods:affiliation>Department of Statistics and Applied Probability, National University of Singapore, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Epidemiology and Public Health, National University of Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="C Tan, Louis" sort="C Tan, Louis" uniqKey="C Tan L" first="Louis" last="C. Tan">Louis C. Tan</name><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Angeles, Dario" sort="Angeles, Dario" uniqKey="Angeles D" first="Dario" last="Angeles">Dario Angeles</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Ho, Patrick" sort="Ho, Patrick" uniqKey="Ho P" first="Patrick" last="Ho">Patrick Ho</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Chen, Meng Ing" sort="Chen, Meng Ing" uniqKey="Chen M" first="Meng-Ling" last="Chen">Meng-Ling Chen</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Lin, Chin Sien" sort="Lin, Chin Sien" uniqKey="Lin C" first="Chin-Hsien" last="Lin">Chin-Hsien Lin</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Mao, Xue E" sort="Mao, Xue E" uniqKey="Mao X" first="Xue-Ye" last="Mao">Xue-Ye Mao</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Chang, Xue I" sort="Chang, Xue I" uniqKey="Chang X" first="Xue-Li" last="Chang">Xue-Li Chang</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Prakash, Kumar M" sort="Prakash, Kumar M" uniqKey="Prakash K" first="Kumar M" last="Prakash">Kumar M. Prakash</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Liu, Jian Un" sort="Liu, Jian Un" uniqKey="Liu J" first="Jian-Jun" last="Liu">Jian-Jun Liu</name><affiliation><mods:affiliation>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Au, Wing Ok" sort="Au, Wing Ok" uniqKey="Au W" first="Wing-Lok" last="Au">Wing-Lok Au</name><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Le, Wei Ong" sort="Le, Wei Ong" uniqKey="Le W" first="Wei-Dong" last="Le">Wei-Dong Le</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</mods:affiliation></affiliation></author><author><name sortKey="Burgunder, Jean Arc" sort="Burgunder, Jean Arc" uniqKey="Burgunder J" first="Jean-Marc" last="Burgunder">Jean-Marc Burgunder</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name><affiliation><mods:affiliation>Clinical Research, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Wu, Ruey Eei" sort="Wu, Ruey Eei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation><affiliation><mods:affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/humu.21225</idno><idno type="url">https://api.istex.fr/document/3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000A00</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title><author><name sortKey="Tan, Eng Ing" sort="Tan, Eng Ing" uniqKey="Tan E" first="Eng-King" last="Tan">Eng-King Tan</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Clinical Research, Singapore General Hospital, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Duke–NUS Graduate Medical School, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Peng, Rong" sort="Peng, Rong" uniqKey="Peng R" first="Rong" last="Peng">Rong Peng</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Teo, Yik Ing" sort="Teo, Yik Ing" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><mods:affiliation>Department of Statistics and Applied Probability, National University of Singapore, Singapore</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Epidemiology and Public Health, National University of Singapore, Singapore</mods:affiliation></affiliation></author><author><name sortKey="C Tan, Louis" sort="C Tan, Louis" uniqKey="C Tan L" first="Louis" last="C. Tan">Louis C. Tan</name><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Angeles, Dario" sort="Angeles, Dario" uniqKey="Angeles D" first="Dario" last="Angeles">Dario Angeles</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Ho, Patrick" sort="Ho, Patrick" uniqKey="Ho P" first="Patrick" last="Ho">Patrick Ho</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Chen, Meng Ing" sort="Chen, Meng Ing" uniqKey="Chen M" first="Meng-Ling" last="Chen">Meng-Ling Chen</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Lin, Chin Sien" sort="Lin, Chin Sien" uniqKey="Lin C" first="Chin-Hsien" last="Lin">Chin-Hsien Lin</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author><author><name sortKey="Mao, Xue E" sort="Mao, Xue E" uniqKey="Mao X" first="Xue-Ye" last="Mao">Xue-Ye Mao</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Chang, Xue I" sort="Chang, Xue I" uniqKey="Chang X" first="Xue-Li" last="Chang">Xue-Li Chang</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation></author><author><name sortKey="Prakash, Kumar M" sort="Prakash, Kumar M" uniqKey="Prakash K" first="Kumar M" last="Prakash">Kumar M. Prakash</name><affiliation><mods:affiliation>Departments of Neurology, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Liu, Jian Un" sort="Liu, Jian Un" uniqKey="Liu J" first="Jian-Jun" last="Liu">Jian-Jun Liu</name><affiliation><mods:affiliation>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Au, Wing Ok" sort="Au, Wing Ok" uniqKey="Au W" first="Wing-Lok" last="Au">Wing-Lok Au</name><affiliation><mods:affiliation>National Neuroscience Institute, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Le, Wei Ong" sort="Le, Wei Ong" uniqKey="Le W" first="Wei-Dong" last="Le">Wei-Dong Le</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</mods:affiliation></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation><mods:affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</mods:affiliation></affiliation></author><author><name sortKey="Burgunder, Jean Arc" sort="Burgunder, Jean Arc" uniqKey="Burgunder J" first="Jean-Marc" last="Burgunder">Jean-Marc Burgunder</name><affiliation><mods:affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurology, University of Bern, Bern, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Zhao, Yi" sort="Zhao, Yi" uniqKey="Zhao Y" first="Yi" last="Zhao">Yi Zhao</name><affiliation><mods:affiliation>Clinical Research, Singapore General Hospital, Singapore</mods:affiliation></affiliation></author><author><name sortKey="Wu, Ruey Eei" sort="Wu, Ruey Eei" uniqKey="Wu R" first="Ruey-Meei" last="Wu">Ruey-Meei Wu</name><affiliation><mods:affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation><affiliation><mods:affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-05">2010-05</date><biblScope unit="volume">31</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="561">561</biblScope><biblScope unit="page" to="568">568</biblScope></imprint><idno type="ISSN">1059-7794</idno></series><idno type="istex">3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF</idno><idno type="DOI">10.1002/humu.21225</idno><idno type="ArticleID">HUMU21225</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Chinese</term><term>Han</term><term>LRRK2</term><term>Parkinson disease</term><term>kinase</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Eng‐King Tan</name><affiliations><json:string>Departments of Neurology, Singapore General Hospital, Singapore</json:string><json:string>Clinical Research, Singapore General Hospital, Singapore</json:string><json:string>National Neuroscience Institute, Singapore</json:string><json:string>Duke–NUS Graduate Medical School, Singapore</json:string><json:string>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</json:string></affiliations></json:item><json:item><name>Rong Peng</name><affiliations><json:string>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</json:string></affiliations></json:item><json:item><name>Yik‐Ying Teo</name><affiliations><json:string>Department of Statistics and Applied Probability, National University of Singapore, Singapore</json:string><json:string>Department of Epidemiology and Public Health, National University of Singapore, Singapore</json:string></affiliations></json:item><json:item><name>Louis C. Tan</name><affiliations><json:string>National Neuroscience Institute, Singapore</json:string></affiliations></json:item><json:item><name>Dario Angeles</name><affiliations><json:string>Departments of Neurology, Singapore General Hospital, Singapore</json:string></affiliations></json:item><json:item><name>Patrick Ho</name><affiliations><json:string>Departments of Neurology, Singapore General Hospital, Singapore</json:string></affiliations></json:item><json:item><name>Meng‐Ling Chen</name><affiliations><json:string>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</json:string></affiliations></json:item><json:item><name>Chin‐Hsien Lin</name><affiliations><json:string>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</json:string></affiliations></json:item><json:item><name>Xue‐Ye Mao</name><affiliations><json:string>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</json:string></affiliations></json:item><json:item><name>Xue‐Li Chang</name><affiliations><json:string>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</json:string></affiliations></json:item><json:item><name>Kumar M Prakash</name><affiliations><json:string>Departments of Neurology, Singapore General Hospital, Singapore</json:string></affiliations></json:item><json:item><name>Jian‐Jun Liu</name><affiliations><json:string>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</json:string></affiliations></json:item><json:item><name>Wing‐Lok Au</name><affiliations><json:string>National Neuroscience Institute, Singapore</json:string></affiliations></json:item><json:item><name>Wei‐Dong Le</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, Texas</json:string></affiliations></json:item><json:item><name>Joseph Jankovic</name><affiliations><json:string>Department of Neurology, Baylor College of Medicine, Houston, Texas</json:string></affiliations></json:item><json:item><name>Jean‐Marc Burgunder</name><affiliations><json:string>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</json:string><json:string>Department of Neurology, University of Bern, Bern, Switzerland</json:string></affiliations></json:item><json:item><name>Yi Zhao</name><affiliations><json:string>Clinical Research, Singapore General Hospital, Singapore</json:string></affiliations></json:item><json:item><name>Ruey‐Meei Wu</name><affiliations><json:string>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</json:string><json:string>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>LRRK2</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Han</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Chinese</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>kinase</value></json:item></subject><articleId><json:string>HUMU21225</json:string></articleId><language><json:string>eng</json:string></language><abstract>We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.</abstract><qualityIndicators><score>7.328</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1322</abstractCharCount><pdfWordCount>5098</pdfWordCount><pdfCharCount>33327</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>194</abstractWordCount></qualityIndicators><title>Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title><genre><json:string>article</json:string></genre><host><volume>31</volume><publisherId><json:string>HUMU</json:string></publisherId><pages><total>8</total><last>568</last><first>561</first></pages><issn><json:string>1059-7794</json:string></issn><issue>5</issue><subject><json:item><value>Research Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1098-1004</json:string></eissn><title>Human Mutation</title><doi><json:string>10.1002/(ISSN)1098-1004</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/humu.21225</json:string></doi><id>3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Communicated by Hamish S. Scott</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title><author><persName><forename type="first">Eng‐King</forename><surname>Tan</surname></persName><note type="biography">Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</note><affiliation>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</affiliation><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation><affiliation>Clinical Research, Singapore General Hospital, Singapore</affiliation><affiliation>National Neuroscience Institute, Singapore</affiliation><affiliation>Duke–NUS Graduate Medical School, Singapore</affiliation><affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation></author><author><persName><forename type="first">Rong</forename><surname>Peng</surname></persName><note type="biography">Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</note><affiliation>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</affiliation><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation></author><author><persName><forename type="first">Yik‐Ying</forename><surname>Teo</surname></persName><note type="biography">Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</note><affiliation>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</affiliation><affiliation>Department of Statistics and Applied Probability, National University of Singapore, Singapore</affiliation><affiliation>Department of Epidemiology and Public Health, National University of Singapore, Singapore</affiliation></author><author><persName><forename type="first">Louis</forename><surname>C. Tan</surname></persName><affiliation>National Neuroscience Institute, Singapore</affiliation></author><author><persName><forename type="first">Dario</forename><surname>Angeles</surname></persName><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation></author><author><persName><forename type="first">Patrick</forename><surname>Ho</surname></persName><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation></author><author><persName><forename type="first">Meng‐Ling</forename><surname>Chen</surname></persName><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation></author><author><persName><forename type="first">Chin‐Hsien</forename><surname>Lin</surname></persName><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation></author><author><persName><forename type="first">Xue‐Ye</forename><surname>Mao</surname></persName><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation></author><author><persName><forename type="first">Xue‐Li</forename><surname>Chang</surname></persName><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation></author><author><persName><forename type="first">Kumar M</forename><surname>Prakash</surname></persName><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation></author><author><persName><forename type="first">Jian‐Jun</forename><surname>Liu</surname></persName><affiliation>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</affiliation></author><author><persName><forename type="first">Wing‐Lok</forename><surname>Au</surname></persName><affiliation>National Neuroscience Institute, Singapore</affiliation></author><author><persName><forename type="first">Wei‐Dong</forename><surname>Le</surname></persName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</affiliation></author><author><persName><forename type="first">Joseph</forename><surname>Jankovic</surname></persName><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</affiliation></author><author><persName><forename type="first">Jean‐Marc</forename><surname>Burgunder</surname></persName><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation><affiliation>Department of Neurology, University of Bern, Bern, Switzerland</affiliation></author><author><persName><forename type="first">Yi</forename><surname>Zhao</surname></persName><affiliation>Clinical Research, Singapore General Hospital, Singapore</affiliation></author><author><persName><forename type="first">Ruey‐Meei</forename><surname>Wu</surname></persName><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation></author></analytic><monogr><title level="j">Human Mutation</title><title level="j" type="abbrev">Hum. Mutat.</title><idno type="pISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><idno type="DOI">10.1002/(ISSN)1098-1004</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-05"></date><biblScope unit="volume">31</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="561">561</biblScope><biblScope unit="page" to="568">568</biblScope></imprint></monogr><idno type="istex">3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF</idno><idno type="DOI">10.1002/humu.21225</idno><idno type="ArticleID">HUMU21225</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>LRRK2</term></item><item><term>Parkinson disease</term></item><item><term>Han</term></item><item><term>Chinese</term></item><item><term>kinase</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-11-11">Received</change><change when="2010-02-01">Registration</change><change when="2010-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF/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>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1098-1004</doi><issn type="print">1059-7794</issn><issn type="electronic">1098-1004</issn><idGroup><id type="product" value="HUMU"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="HUMAN MUTATION">Human Mutation</title><title type="short">Hum. Mutat.</title></titleGroup></publicationMeta><publicationMeta level="part" position="50"><doi origin="wiley" registered="yes">10.1002/humu.v31:5</doi><numberingGroup><numbering type="journalVolume" number="31">31</numbering><numbering type="journalIssue">5</numbering></numberingGroup><coverDate startDate="2010-05">May 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="8" status="forIssue"><doi origin="wiley" registered="yes">10.1002/humu.21225</doi><idGroup><id type="unit" value="HUMU21225"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="publisher">© 2010 Wiley‐Liss, Inc.</copyright><eventGroup><event type="manuscriptReceived" date="2009-11-11"></event><event type="manuscriptAccepted" date="2010-02-01"></event><event type="publishedOnlineAccepted" date="2010-02-25"></event><event type="firstOnline" date="2010-02-25"></event><event type="publishedOnlineFinalForm" date="2010-04-29"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.3.10 mode:FullText source:HeaderRef result:HeaderRef" date="2010-06-24"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-27"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-23"></event></eventGroup><numberingGroup><numbering type="pageFirst">561</numbering><numbering type="pageLast">568</numbering></numberingGroup><correspondenceTo><lineatedText><line>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108</line><line>Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</line></lineatedText></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:HUMU.HUMU21225.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="4"></count><count type="referenceTotal" number="34"></count></countGroup><titleGroup><title type="main" xml:lang="en">Multiple <i>LRRK2</i> variants modulate risk of Parkinson disease: a chinese multicenter study<link href="#fn1"></link></title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2 #af3 #af4" corresponding="yes" noteRef="#fn2"><personName><givenNames>Eng‐King</givenNames><familyName>Tan</familyName></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af5" noteRef="#fn2"><personName><givenNames>Rong</givenNames><familyName>Peng</familyName></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af6 #af7" noteRef="#fn2"><personName><givenNames>Yik‐Ying</givenNames><familyName>Teo</familyName></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Louis</givenNames><familyName>C. Tan</familyName></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Dario</givenNames><familyName>Angeles</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Patrick</givenNames><familyName>Ho</familyName></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Meng‐Ling</givenNames><familyName>Chen</familyName></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Chin‐Hsien</givenNames><familyName>Lin</familyName></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Xue‐Ye</givenNames><familyName>Mao</familyName></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Xue‐Li</givenNames><familyName>Chang</familyName></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Kumar M</givenNames><familyName>Prakash</familyName></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Jian‐Jun</givenNames><familyName>Liu</familyName></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Wing‐Lok</givenNames><familyName>Au</familyName></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Wei‐Dong</givenNames><familyName>Le</familyName></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af10"><personName><givenNames>Joseph</givenNames><familyName>Jankovic</familyName></personName></creator><creator xml:id="au16" creatorRole="author" affiliationRef="#af5 #af11"><personName><givenNames>Jean‐Marc</givenNames><familyName>Burgunder</familyName></personName></creator><creator xml:id="au17" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Yi</givenNames><familyName>Zhao</familyName></personName></creator><creator xml:id="au18" creatorRole="author" affiliationRef="#af8" corresponding="yes"><personName><givenNames>Ruey‐Meei</givenNames><familyName>Wu</familyName></personName><contactDetails><email>robinwu@ntu.edu.tw</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="SG" type="organization"><unparsedAffiliation>Departments of Neurology, Singapore General Hospital, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="SG" type="organization"><unparsedAffiliation>Clinical Research, Singapore General Hospital, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="SG" type="organization"><unparsedAffiliation>National Neuroscience Institute, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="SG" type="organization"><unparsedAffiliation>Duke–NUS Graduate Medical School, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="CN" type="organization"><unparsedAffiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="SG" type="organization"><unparsedAffiliation>Department of Statistics and Applied Probability, National University of Singapore, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="SG" type="organization"><unparsedAffiliation>Department of Epidemiology and Public Health, National University of Singapore, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="TW" type="organization"><unparsedAffiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="SG" type="organization"><unparsedAffiliation>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="CH" type="organization"><unparsedAffiliation>Department of Neurology, University of Bern, Bern, Switzerland</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1"><i>LRRK2</i></keyword><keyword xml:id="kwd2">Parkinson disease</keyword><keyword xml:id="kwd3">Han</keyword><keyword xml:id="kwd4">Chinese</keyword><keyword xml:id="kwd5">kinase</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>We and others found two polymorphic <i>LRRK2</i> (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple <i>LRRK2</i> variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Communicated by Hamish S. Scott</p></note><note xml:id="fn2"><p>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Multiple</title></titleInfo><name type="personal"><namePart type="given">Eng‐King</namePart><namePart type="family">Tan</namePart><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation><affiliation>Clinical Research, Singapore General Hospital, Singapore</affiliation><affiliation>National Neuroscience Institute, Singapore</affiliation><affiliation>Duke–NUS Graduate Medical School, Singapore</affiliation><description>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</description><affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rong</namePart><namePart type="family">Peng</namePart><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation><description>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yik‐Ying</namePart><namePart type="family">Teo</namePart><affiliation>Department of Statistics and Applied Probability, National University of Singapore, Singapore</affiliation><affiliation>Department of Epidemiology and Public Health, National University of Singapore, Singapore</affiliation><description>Eng King‐Tan, Rong Peng, and Yik‐Ying Teo are considered joint first authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Louis</namePart><namePart type="family">C. Tan</namePart><affiliation>National Neuroscience Institute, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dario</namePart><namePart type="family">Angeles</namePart><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Ho</namePart><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Meng‐Ling</namePart><namePart type="family">Chen</namePart><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chin‐Hsien</namePart><namePart type="family">Lin</namePart><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xue‐Ye</namePart><namePart type="family">Mao</namePart><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Xue‐Li</namePart><namePart type="family">Chang</namePart><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kumar M</namePart><namePart type="family">Prakash</namePart><affiliation>Departments of Neurology, Singapore General Hospital, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jian‐Jun</namePart><namePart type="family">Liu</namePart><affiliation>Human Genetics, Genome Institute of Singapore, A*STAR, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wing‐Lok</namePart><namePart type="family">Au</namePart><affiliation>National Neuroscience Institute, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wei‐Dong</namePart><namePart type="family">Le</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joseph</namePart><namePart type="family">Jankovic</namePart><affiliation>Department of Neurology, Baylor College of Medicine, Houston, Texas</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Marc</namePart><namePart type="family">Burgunder</namePart><affiliation>Department of Neurology, West China Hospital, Sichuan University, Chengdu, China</affiliation><affiliation>Department of Neurology, University of Bern, Bern, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yi</namePart><namePart type="family">Zhao</namePart><affiliation>Clinical Research, Singapore General Hospital, Singapore</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ruey‐Meei</namePart><namePart type="family">Wu</namePart><affiliation>Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><affiliation>Eng‐King Tan, Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169108Ruey‐Meei Wu, Department of Neurology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-05</dateIssued><dateCaptured encoding="w3cdtf">2009-11-11</dateCaptured><dateValid encoding="w3cdtf">2010-02-01</dateValid><copyrightDate encoding="w3cdtf">2010</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="figures">3</extent><extent unit="tables">4</extent><extent unit="references">34</extent></physicalDescription><abstract lang="en">We and others found two polymorphic LRRK2 (leucine‐rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first sequenced the coding regions in young onset and familial PD patients and identified 59 variants. We then examined these variants in 250 patients and 250 control subjects. Among the 17 polymorphic variants, five demonstrated different frequency in cases versus controls and were considered in a larger sample of 1,363 patients and 1,251 control subjects. The relative risk of an individual with both p.G2385R and p.R1628P is about 1.9, and this is reduced to 1.5–1.6 if the individual also carries rs7133914:G>C; p.R1398H or rs7308720:C>A: p.N551K. The risk of a carrier with p.R1628P is largely negated if the individual also carries p.R1398H or p.N551K. In dopaminergic neuronal lines, p.R1398H had significantly lower kinase activity, whereas p.G2385R and p.R1628P showed higher kinase activity than wild type. We provided the first evidence that multiple LRRK2 variants exert an individual effect and together modulate the risk of PD among Chinese. Hum Mutat 31:561–568, 2010. © 2010 Wiley‐Liss, Inc.</abstract><note type="content">*Communicated by Hamish S. Scott</note><subject lang="en"><genre>Keywords</genre><topic>LRRK2</topic><topic>Parkinson disease</topic><topic>Han</topic><topic>Chinese</topic><topic>kinase</topic></subject><relatedItem type="host"><titleInfo><title>Human Mutation</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mutat.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1059-7794</identifier><identifier type="eISSN">1098-1004</identifier><identifier type="DOI">10.1002/(ISSN)1098-1004</identifier><identifier type="PublisherID">HUMU</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>31</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>561</start><end>568</end><total>8</total></extent></part></relatedItem><identifier type="istex">3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF</identifier><identifier type="DOI">10.1002/humu.21225</identifier><identifier type="ArticleID">HUMU21225</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A00 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000A00 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:3EE7DBF3D18D5DBD5BDE0DD45A47620505FDC4FF
|texte= Multiple LRRK2 variants modulate risk of Parkinson disease: a chinese multicenter study
}}
| This area was generated with Dilib version V0.6.23. |  |