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The protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants

dc.creatorHeckman, M. G.en
dc.creatorElbaz, A.en
dc.creatorSoto-Ortolaza, A. I.en
dc.creatorSerie, D. J.en
dc.creatorAasly, J. O.en
dc.creatorAnnesi, G.en
dc.creatorAuburger, G.en
dc.creatorBacon, J. A.en
dc.creatorBoczarska-Jedynak, M.en
dc.creatorBozi, M.en
dc.creatorBrighina, L.en
dc.creatorChartier-Harlin, M. C.en
dc.creatorDardiotis, E.en
dc.creatorDestée, A.en
dc.creatorFerrarese, C.en
dc.creatorFerraris, A.en
dc.creatorFiske, B.en
dc.creatorGispert, S.en
dc.creatorHadjigeorgiou, G. M.en
dc.creatorHattori, N.en
dc.creatorIoannidis, J. P. A.en
dc.creatorJasinska-Myga, B.en
dc.creatorJeon, B. S.en
dc.creatorKim, Y. J.en
dc.creatorKlein, C.en
dc.creatorKruger, R.en
dc.creatorKyratzi, E.en
dc.creatorLin, C. H.en
dc.creatorLohmann, K.en
dc.creatorLoriot, M. A.en
dc.creatorLynch, T.en
dc.creatorMellick, G. D.en
dc.creatorMutez, E.en
dc.creatorOpala, G.en
dc.creatorPark, S. S.en
dc.creatorPetrucci, S.en
dc.creatorQuattrone, A.en
dc.creatorSharma, M.en
dc.creatorSilburn, P. A.en
dc.creatorSohn, Y. H.en
dc.creatorStefanis, L.en
dc.creatorTadic, V.en
dc.creatorTomiyama, H.en
dc.creatorUitti, R. J.en
dc.creatorValente, E. M.en
dc.creatorVassilatis, D. K.en
dc.creatorVilariño-Güell, C.en
dc.creatorWhite, L. R.en
dc.creatorWirdefeldt, K.en
dc.creatorWszolek, Z. K.en
dc.creatorWu, R. M.en
dc.creatorXiromerisiou, G.en
dc.creatorMaraganore, D. M.en
dc.creatorFarrer, M. J.en
dc.creatorRoss, O. A.en
dc.date.accessioned2015-11-23T10:30:06Z
dc.date.available2015-11-23T10:30:06Z
dc.date.issued2014
dc.identifier10.1016/j.neurobiolaging.2013.07.013
dc.identifier.issn1974580
dc.identifier.urihttp://hdl.handle.net/11615/28487
dc.description.abstractThe best validated susceptibility variants for Parkinson's disease are located in the α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and rs2583988), the MAPT H1-haplotype-defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (n= 10,322) and Asian (n= 2289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p ≥ 0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations. © 2014 Elsevier Inc.en
dc.sourceNeurobiology of Agingen
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-84885187895&partnerID=40&md5=c295b7406d4cd1619f495c332cc01bee
dc.subjectGeneticsen
dc.subjectInteractionen
dc.subjectLRRK2en
dc.subjectMAPTen
dc.subjectParkinson's diseaseen
dc.subjectSNCAen
dc.subjectalpha synucleinen
dc.subjectleucine rich repeat kinase 2en
dc.subjecttau proteinen
dc.subjectadulten
dc.subjectarticleen
dc.subjectAsianen
dc.subjectCaucasianen
dc.subjectcontrolled studyen
dc.subjectethnic differenceen
dc.subjectfemaleen
dc.subjectgeneen
dc.subjectgene interactionen
dc.subjectgenetic analysisen
dc.subjectgenetic variabilityen
dc.subjectgenotypeen
dc.subjecthaplotypeen
dc.subjecthumanen
dc.subjectLRRK2 geneen
dc.subjectmajor clinical studyen
dc.subjectmaleen
dc.subjectMAPT geneen
dc.subjectneuroprotectionen
dc.subjectParkinson diseaseen
dc.subjectpriority journalen
dc.subjectSNCA geneen
dc.subjectAdolescenten
dc.subjectAgeden
dc.subjectAged, 80 and overen
dc.subjectalpha-Synucleinen
dc.subjectAsian Continental Ancestry Groupen
dc.subjectEuropean Continental Ancestry Groupen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenetic Variationen
dc.subjectHaplotypesen
dc.subjectHumansen
dc.subjectMiddle Ageden
dc.subjectProtein-Serine-Threonine Kinasesen
dc.subjectRisken
dc.subjecttau Proteinsen
dc.subjectYoung Adulten
dc.titleThe protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variantsen
dc.typejournalArticleen


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