LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease
Identifieur interne : 000148 ( Main/Corpus ); précédent : 000147; suivant : 000149LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease
Auteurs : Cyrus P. Zabetian ; Mitsutoshi Yamamoto ; Alexis N. Lopez ; Hiroshi Ujike ; Ignacio F. Mata ; Yuishin Izumi ; Ryuji Kaji ; Hirofumi Maruyama ; Hiroyuki Morino ; Masaya Oda ; Carolyn M. Hutter ; Karen L. Edwards ; Gerard D. Schellenberg ; Debby W. Tsuang ; Dora Yearout ; Eric B. Larson ; Hideshi KawakamiSource :
- Movement Disorders [ 0885-3185 ] ; 2009-05-15.
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Abstract
Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10−4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society
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DOI: 10.1002/mds.22514
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Zabetian</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Northwest Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name><affiliation><mods:affiliation>Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan</mods:affiliation></affiliation></author><author><name sortKey="Lopez, Alexis N" sort="Lopez, Alexis N" uniqKey="Lopez A" first="Alexis N." last="Lopez">Alexis N. 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Tsuang</name><affiliation><mods:affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Larson, Eric B" sort="Larson, Eric B" uniqKey="Larson E" first="Eric B." last="Larson">Eric B. Larson</name><affiliation><mods:affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Center for Health Studies, Group Health Cooperative, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><affiliation><mods:affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:7FEA2A8837CC8A10BE90CD8DD556462988FF952D</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/mds.22514</idno><idno type="url">https://api.istex.fr/document/7FEA2A8837CC8A10BE90CD8DD556462988FF952D/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000148</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease</title><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Northwest Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name><affiliation><mods:affiliation>Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan</mods:affiliation></affiliation></author><author><name sortKey="Lopez, Alexis N" sort="Lopez, Alexis N" uniqKey="Lopez A" first="Alexis N." last="Lopez">Alexis N. Lopez</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Ujike, Hiroshi" sort="Ujike, Hiroshi" uniqKey="Ujike H" first="Hiroshi" last="Ujike">Hiroshi Ujike</name><affiliation><mods:affiliation>Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</mods:affiliation></affiliation></author><author><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Izumi, Yuishin" sort="Izumi, Yuishin" uniqKey="Izumi Y" first="Yuishin" last="Izumi">Yuishin Izumi</name><affiliation><mods:affiliation>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</mods:affiliation></affiliation></author><author><name sortKey="Kaji, Ryuji" sort="Kaji, Ryuji" uniqKey="Kaji R" first="Ryuji" last="Kaji">Ryuji Kaji</name><affiliation><mods:affiliation>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</mods:affiliation></affiliation></author><author><name sortKey="Maruyama, Hirofumi" sort="Maruyama, Hirofumi" uniqKey="Maruyama H" first="Hirofumi" last="Maruyama">Hirofumi Maruyama</name><affiliation><mods:affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</mods:affiliation></affiliation></author><author><name sortKey="Morino, Hiroyuki" sort="Morino, Hiroyuki" uniqKey="Morino H" first="Hiroyuki" last="Morino">Hiroyuki Morino</name><affiliation><mods:affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</mods:affiliation></affiliation></author><author><name sortKey="Oda, Masaya" sort="Oda, Masaya" uniqKey="Oda M" first="Masaya" last="Oda">Masaya Oda</name><affiliation><mods:affiliation>Department of Neurology, Sumitomo Hospital, Osaka, Japan</mods:affiliation></affiliation></author><author><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name><affiliation><mods:affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Edwards, Karen L" sort="Edwards, Karen L" uniqKey="Edwards K" first="Karen L." last="Edwards">Karen L. Edwards</name><affiliation><mods:affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Tsuang, Debby W" sort="Tsuang, Debby W" uniqKey="Tsuang D" first="Debby W." last="Tsuang">Debby W. Tsuang</name><affiliation><mods:affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation><mods:affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Larson, Eric B" sort="Larson, Eric B" uniqKey="Larson E" first="Eric B." last="Larson">Eric B. Larson</name><affiliation><mods:affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</mods:affiliation></affiliation><affiliation><mods:affiliation>Center for Health Studies, Group Health Cooperative, Seattle, Washington</mods:affiliation></affiliation></author><author><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><affiliation><mods:affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-05-15">2009-05-15</date><biblScope unit="volume">24</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1034">1034</biblScope><biblScope unit="page" to="1041">1041</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">7FEA2A8837CC8A10BE90CD8DD556462988FF952D</idno><idno type="DOI">10.1002/mds.22514</idno><idno type="ArticleID">MDS22514</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson</term><term>mutation</term><term>polymorphism</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10−4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Cyrus P. Zabetian MD, MS</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Northwest Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Mitsutoshi Yamamoto MD, PhD</name><affiliations><json:string>Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan</json:string></affiliations></json:item><json:item><name>Alexis N. Lopez BS</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Hiroshi Ujike MD, PhD</name><affiliations><json:string>Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</json:string></affiliations></json:item><json:item><name>Ignacio F. Mata PhD</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Yuishin Izumi MD</name><affiliations><json:string>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</json:string></affiliations></json:item><json:item><name>Ryuji Kaji MD</name><affiliations><json:string>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</json:string></affiliations></json:item><json:item><name>Hirofumi Maruyama MD</name><affiliations><json:string>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</json:string></affiliations></json:item><json:item><name>Hiroyuki Morino MD</name><affiliations><json:string>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</json:string></affiliations></json:item><json:item><name>Masaya Oda MD</name><affiliations><json:string>Department of Neurology, Sumitomo Hospital, Osaka, Japan</json:string></affiliations></json:item><json:item><name>Carolyn M. Hutter PhD</name><affiliations><json:string>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Karen L. Edwards PhD</name><affiliations><json:string>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Gerard D. Schellenberg PhD</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Debby W. Tsuang MD, MSc</name><affiliations><json:string>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string><json:string>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Dora Yearout BS</name><affiliations><json:string>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Eric B. Larson MD, MPH</name><affiliations><json:string>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</json:string><json:string>Center for Health Studies, Group Health Cooperative, Seattle, Washington</json:string></affiliations></json:item><json:item><name>Hideshi Kawakami MD, PhD</name><affiliations><json:string>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>mutation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>polymorphism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson</value></json:item></subject><articleId><json:string>MDS22514</json:string></articleId><language><json:string>eng</json:string></language><abstract>Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10−4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society</abstract><qualityIndicators><score>7.109</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>3</keywordCount><abstractCharCount>1339</abstractCharCount><pdfWordCount>4649</pdfWordCount><pdfCharCount>29693</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>205</abstractWordCount></qualityIndicators><title>LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease</title><genre><json:string>article</json:string></genre><host><volume>24</volume><publisherId><json:string>MDS</json:string></publisherId><pages><total>8</total><last>1041</last><first>1034</first></pages><issn><json:string>0885-3185</json:string></issn><issue>7</issue><subject><json:item><value>Research 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uri="https://api.istex.fr/document/7FEA2A8837CC8A10BE90CD8DD556462988FF952D/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2009</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: None reported.</note><note>American Parkinson Disease Association</note><note>Research Grant to Dr Zabetian</note><note>National Institutes of Health</note><note>National Institute of Neurological Disorders and Stroke - No. K08 NS044138;</note><note>Department of Veterans Affairs</note><note>Merit Review Award to Dr Zabetian</note><note>Smoking Research Foundation</note><note>Biomedical Research</note><note>Veterans Integrated Service Network 20 Geriatric</note><note>Mental Illness</note><note>Parkinson's Disease Research Education and Clinical Centers</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease</title><author><persName><forename type="first">Cyrus P.</forename><surname>Zabetian</surname></persName><roleName type="degree">MD, MS</roleName><note type="correspondence"><p>Correspondence: Geriatric Research Education and Clinical Center S‐182, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, Washington 98108===</p></note><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Northwest Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Mitsutoshi</forename><surname>Yamamoto</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan</affiliation></author><author><persName><forename type="first">Alexis N.</forename><surname>Lopez</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Hiroshi</forename><surname>Ujike</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</affiliation></author><author><persName><forename type="first">Ignacio F.</forename><surname>Mata</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Yuishin</forename><surname>Izumi</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</affiliation></author><author><persName><forename type="first">Ryuji</forename><surname>Kaji</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Clinical Neuroscience, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan</affiliation></author><author><persName><forename type="first">Hirofumi</forename><surname>Maruyama</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</affiliation></author><author><persName><forename type="first">Hiroyuki</forename><surname>Morino</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</affiliation></author><author><persName><forename type="first">Masaya</forename><surname>Oda</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Sumitomo Hospital, Osaka, Japan</affiliation></author><author><persName><forename type="first">Carolyn M.</forename><surname>Hutter</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</affiliation></author><author><persName><forename type="first">Karen L.</forename><surname>Edwards</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</affiliation></author><author><persName><forename type="first">Gerard D.</forename><surname>Schellenberg</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington</affiliation></author><author><persName><forename type="first">Debby W.</forename><surname>Tsuang</surname></persName><roleName type="degree">MD, MSc</roleName><affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</affiliation></author><author><persName><forename type="first">Dora</forename><surname>Yearout</surname></persName><roleName type="degree">BS</roleName><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation></author><author><persName><forename type="first">Eric B.</forename><surname>Larson</surname></persName><roleName type="degree">MD, MPH</roleName><affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Center for Health Studies, Group Health Cooperative, Seattle, Washington</affiliation></author><author><persName><forename type="first">Hideshi</forename><surname>Kawakami</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. 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To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10−4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>mutation</term></item><item><term>polymorphism</term></item><item><term>Parkinson</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="2008-09-29">Received</change><change when="2009-01-30">Registration</change><change when="2009-05-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/7FEA2A8837CC8A10BE90CD8DD556462988FF952D/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)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. 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href="file:MDS.MDS22514.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="4"></count><count type="referenceTotal" number="37"></count><count type="wordTotal" number="6102"></count></countGroup><titleGroup><title type="main" xml:lang="en"><i>LRRK2</i> mutations and risk variants in Japanese patients with Parkinson's disease<link href="#fn1"></link></title><title type="short" xml:lang="en"><fi>LRRK2</fi> in Japan</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2 #af3 #af4" corresponding="yes"><personName><givenNames>Cyrus P.</givenNames><familyName>Zabetian</familyName><degrees>MD, MS</degrees></personName><contactDetails><email>zabetian@u.washington.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Mitsutoshi</givenNames><familyName>Yamamoto</familyName><degrees>MD, 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xml:id="af10" countryCode="US" type="organization"><unparsedAffiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="US" type="organization"><unparsedAffiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="US" type="organization"><unparsedAffiliation>Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af13" countryCode="US" type="organization"><unparsedAffiliation>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</unparsedAffiliation></affiliation><affiliation xml:id="af14" countryCode="US" type="organization"><unparsedAffiliation>Center for Health Studies, Group Health Cooperative, Seattle, Washington</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">mutation</keyword><keyword xml:id="kwd2">polymorphism</keyword><keyword xml:id="kwd3">Parkinson</keyword></keywordGroup><fundingInfo><fundingAgency>American Parkinson Disease Association</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Research Grant to Dr Zabetian</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institutes of Health</fundingAgency></fundingInfo><fundingInfo><fundingAgency>National Institute of Neurological Disorders and Stroke</fundingAgency><fundingNumber>K08 NS044138</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Department of Veterans Affairs</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Merit Review Award to Dr Zabetian</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Smoking Research Foundation</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Biomedical Research</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Veterans Integrated Service Network 20 Geriatric</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Mental Illness</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Parkinson's Disease Research Education and Clinical Centers</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Mutations in the leucine‐rich repeat kinase 2 (<i>LRRK2</i>) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about <i>LRRK2</i> mutations and susceptibility alleles in Asians. To address this issue, we sequenced the <i>LRRK2</i> coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; <i>P</i> = 3.3 × 10<sup>−4</sup>) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, <i>LRRK2</i> mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: None reported.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>LRRK2 in Japan</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>mutations and risk variants in Japanese patients with Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Cyrus P.</namePart><namePart type="family">Zabetian</namePart><namePart type="termsOfAddress">MD, MS</namePart><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, 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type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexis N.</namePart><namePart type="family">Lopez</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hiroshi</namePart><namePart type="family">Ujike</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ignacio F.</namePart><namePart type="family">Mata</namePart><namePart 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Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hirofumi</namePart><namePart type="family">Maruyama</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hiroyuki</namePart><namePart type="family">Morino</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Masaya</namePart><namePart type="family">Oda</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Sumitomo Hospital, Osaka, Japan</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carolyn M.</namePart><namePart type="family">Hutter</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karen L.</namePart><namePart type="family">Edwards</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gerard D.</namePart><namePart type="family">Schellenberg</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Debby W.</namePart><namePart type="family">Tsuang</namePart><namePart type="termsOfAddress">MD, MSc</namePart><affiliation>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><affiliation>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dora</namePart><namePart type="family">Yearout</namePart><namePart type="termsOfAddress">BS</namePart><affiliation>Department of Neurology, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eric B.</namePart><namePart type="family">Larson</namePart><namePart type="termsOfAddress">MD, MPH</namePart><affiliation>Department of Medicine, University of Washington School of Medicine, Seattle, Washington</affiliation><affiliation>Center for Health Studies, Group Health Cooperative, Seattle, Washington</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hideshi</namePart><namePart type="family">Kawakami</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan</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">2009-05-15</dateIssued><dateCaptured encoding="w3cdtf">2008-09-29</dateCaptured><dateValid encoding="w3cdtf">2009-01-30</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">2</extent><extent unit="tables">4</extent><extent unit="references">37</extent><extent unit="words">6102</extent></physicalDescription><abstract lang="en">Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10−4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: None reported.</note><note type="funding">American Parkinson Disease Association</note><note type="funding">Research Grant to Dr Zabetian</note><note type="funding">National Institutes of Health</note><note type="funding">National Institute of Neurological Disorders and Stroke - No. K08 NS044138; </note><note type="funding">Department of Veterans Affairs</note><note type="funding">Merit Review Award to Dr Zabetian</note><note type="funding">Smoking Research Foundation</note><note type="funding">Biomedical Research</note><note type="funding">Veterans Integrated Service Network 20 Geriatric</note><note type="funding">Mental Illness</note><note type="funding">Parkinson's Disease Research Education and Clinical Centers</note><subject lang="en"><genre>Keywords</genre><topic>mutation</topic><topic>polymorphism</topic><topic>Parkinson</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>1034</start><end>1041</end><total>8</total></extent></part></relatedItem><identifier type="istex">7FEA2A8837CC8A10BE90CD8DD556462988FF952D</identifier><identifier type="DOI">10.1002/mds.22514</identifier><identifier type="ArticleID">MDS22514</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Movement Disorder Society</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)
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