| Literature DB >> 23962496 |
Michael G Heckman1, Alexis Elbaz, Alexandra I Soto-Ortolaza, Daniel J Serie, Jan O Aasly, Grazia Annesi, Georg Auburger, Justin A Bacon, Magdalena Boczarska-Jedynak, Maria Bozi, Laura Brighina, Marie-Christine Chartier-Harlin, Efthimios Dardiotis, Alain Destée, Carlo Ferrarese, Alessandro Ferraris, Brian Fiske, Suzana Gispert, Georgios M Hadjigeorgiou, Nobutaka Hattori, John P A Ioannidis, Barbara Jasinska-Myga, Beom S Jeon, Yun Joong Kim, Christine Klein, Rejko Kruger, Elli Kyratzi, Chin-Hsien Lin, Katja Lohmann, Marie-Anne Loriot, Timothy Lynch, George D Mellick, Eugénie Mutez, Grzegorz Opala, Sung Sup Park, Simona Petrucci, Aldo Quattrone, Manu Sharma, Peter A Silburn, Young Ho Sohn, Leonidas Stefanis, Vera Tadic, Hiroyuki Tomiyama, Ryan J Uitti, Enza Maria Valente, Demetrios K Vassilatis, Carles Vilariño-Güell, Linda R White, Karin Wirdefeldt, Zbigniew K Wszolek, Ruey-Meei Wu, Georgia Xiromerisiou, Demetrius M Maraganore, Matthew J Farrer, Owen A Ross.
Abstract
The 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.Entities:
Keywords: Genetics; Interaction; LRRK2; MAPT; Parkinson's disease; SNCA
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Year: 2013 PMID： 23962496 PMCID： PMC3829604 DOI： 10.1016/j.neurobiolaging.2013.07.013
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673