LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease
Identifieur interne : 000A53 ( Main/Exploration ); précédent : 000A52; suivant : 000A54LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease
Auteurs : Cyrus P. Zabetian [États-Unis] ; Mitsutoshi Yamamoto [Japon] ; Alexis N. Lopez [États-Unis] ; Hiroshi Ujike [Japon] ; Ignacio F. Mata [États-Unis] ; Yuishin Izumi [Japon] ; Ryuji Kaji [Japon] ; Hirofumi Maruyama [Japon] ; Hiroyuki Morino [Japon] ; Masaya Oda [Japon] ; Carolyn M. Hutter [États-Unis] ; Karen L. Edwards [États-Unis] ; Gerard D. Schellenberg [États-Unis] ; Debby W. Tsuang [États-Unis] ; Dora Yearout [États-Unis] ; Eric B. Larson [États-Unis] ; Hideshi Kawakami [Japon]Source :
- 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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Neurology, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Northwest Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu</wicri:regionArea><wicri:noRegion>Takamatsu</wicri:noRegion></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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Hutter</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle</wicri:cityArea></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle</wicri:cityArea></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Neurology, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Medicine, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Pharmacology, University of Washington School of Medicine, Seattle</wicri:cityArea></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Mental Illness Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Neurology, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle</wicri:cityArea></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 wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Medicine, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Center for Health Studies, Group Health Cooperative, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima</wicri:regionArea><wicri:noRegion>Hiroshima</wicri:noRegion></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><affiliations><list><country><li>Japon</li><li>États-Unis</li></country><region><li>Washington (État)</li></region></list><tree><country name="États-Unis"><region name="Washington (État)"><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name></region><name sortKey="Edwards, Karen L" sort="Edwards, Karen L" uniqKey="Edwards K" first="Karen L." last="Edwards">Karen L. Edwards</name><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name><name sortKey="Larson, Eric B" sort="Larson, Eric B" uniqKey="Larson E" first="Eric B." last="Larson">Eric B. Larson</name><name sortKey="Larson, Eric B" sort="Larson, Eric B" uniqKey="Larson E" first="Eric B." last="Larson">Eric B. Larson</name><name sortKey="Lopez, Alexis N" sort="Lopez, Alexis N" uniqKey="Lopez A" first="Alexis N." last="Lopez">Alexis N. Lopez</name><name sortKey="Lopez, Alexis N" sort="Lopez, Alexis N" uniqKey="Lopez A" first="Alexis N." last="Lopez">Alexis N. Lopez</name><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><name sortKey="Mata, Ignacio F" sort="Mata, Ignacio F" uniqKey="Mata I" first="Ignacio F." last="Mata">Ignacio F. Mata</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Tsuang, Debby W" sort="Tsuang, Debby W" uniqKey="Tsuang D" first="Debby W." last="Tsuang">Debby W. Tsuang</name><name sortKey="Tsuang, Debby W" sort="Tsuang, Debby W" uniqKey="Tsuang D" first="Debby W." last="Tsuang">Debby W. Tsuang</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name></country><country name="Japon"><noRegion><name sortKey="Yamamoto, Mitsutoshi" sort="Yamamoto, Mitsutoshi" uniqKey="Yamamoto M" first="Mitsutoshi" last="Yamamoto">Mitsutoshi Yamamoto</name></noRegion><name sortKey="Izumi, Yuishin" sort="Izumi, Yuishin" uniqKey="Izumi Y" first="Yuishin" last="Izumi">Yuishin Izumi</name><name sortKey="Kaji, Ryuji" sort="Kaji, Ryuji" uniqKey="Kaji R" first="Ryuji" last="Kaji">Ryuji Kaji</name><name sortKey="Kawakami, Hideshi" sort="Kawakami, Hideshi" uniqKey="Kawakami H" first="Hideshi" last="Kawakami">Hideshi Kawakami</name><name sortKey="Maruyama, Hirofumi" sort="Maruyama, Hirofumi" uniqKey="Maruyama H" first="Hirofumi" last="Maruyama">Hirofumi Maruyama</name><name sortKey="Morino, Hiroyuki" sort="Morino, Hiroyuki" uniqKey="Morino H" first="Hiroyuki" last="Morino">Hiroyuki Morino</name><name sortKey="Oda, Masaya" sort="Oda, Masaya" uniqKey="Oda M" first="Masaya" last="Oda">Masaya Oda</name><name sortKey="Ujike, Hiroshi" sort="Ujike, Hiroshi" uniqKey="Ujike H" first="Hiroshi" last="Ujike">Hiroshi Ujike</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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