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Elbaz, Alexis; Ross, Owen A.; Ioannidis, John P. A.; Soto‐Ortolaza, Alexandra I.; Moisan, Frédéric; Aasly, Jan; Annesi, Grazia; Bozi, Maria; Brighina, Laura; Chartier‐Harlin, Marie‐Christine; Destée, Alain; Ferrarese, Carlo; Ferraris, Alessandro; Gibson, J. Mark; Gispert, Suzana; Hadjigeorgiou, Georgios M.; Jasinska‐Myga, Barbara; Klein, Christine; Krüger, Rejko; Lambert, Jean‐Charles; Lohmann, Katja; van de Loo, Simone; Loriot, Marie‐Anne; Lynch, Timothy; [...]

Independent and joint effects of the MAPT and SNCA genes in Parkinson disease

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  • Medientyp: E-Artikel
  • Titel: Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
  • Beteiligte: Elbaz, Alexis; Ross, Owen A.; Ioannidis, John P. A.; Soto‐Ortolaza, Alexandra I.; Moisan, Frédéric; Aasly, Jan; Annesi, Grazia; Bozi, Maria; Brighina, Laura; Chartier‐Harlin, Marie‐Christine; Destée, Alain; Ferrarese, Carlo; Ferraris, Alessandro; Gibson, J. Mark; Gispert, Suzana; Hadjigeorgiou, Georgios M.; Jasinska‐Myga, Barbara; Klein, Christine; Krüger, Rejko; Lambert, Jean‐Charles; Lohmann, Katja; van de Loo, Simone; Loriot, Marie‐Anne; Lynch, Timothy; [...]
  • Erschienen: Wiley, 2011
  • Erschienen in: Annals of Neurology
  • Sprache: Englisch
  • DOI: 10.1002/ana.22321
  • ISSN: 0364-5134; 1531-8249
  • Schlagwörter: Neurology (clinical) ; Neurology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective:</jats:title><jats:p>We studied the independent and joint effects of the genes encoding alpha‐synuclein (<jats:italic>SNCA</jats:italic>) and microtubule‐associated protein tau (<jats:italic>MAPT</jats:italic>) in Parkinson disease (PD) as part of a large meta‐analysis of individual data from case–control studies participating in the Genetic Epidemiology of Parkinson's Disease (GEO‐PD) consortium.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Participants of Caucasian ancestry were genotyped for a total of 4 <jats:italic>SNCA</jats:italic> (rs2583988, rs181489, rs356219, rs11931074) and 2 <jats:italic>MAPT</jats:italic> (rs1052553, rs242557) single nucleotide polymorphism (SNPs). Individual and joint effects of <jats:italic>SNCA</jats:italic> and <jats:italic>MAPT</jats:italic> SNPs were investigated using fixed‐ and random‐effects logistic regression models. Interactions were studied on both a multiplicative and an additive scale, and using a case–control and case‐only approach.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Fifteen GEO‐PD sites contributed a total of 5,302 cases and 4,161 controls. All 4 <jats:italic>SNCA</jats:italic> SNPs and the <jats:italic>MAPT</jats:italic> H1‐haplotype–defining SNP (rs1052553) displayed a highly significant marginal association with PD at the significance level adjusted for multiple comparisons. For <jats:italic>SNCA</jats:italic>, the strongest associations were observed for SNPs located at the 3′ end of the gene. There was no evidence of statistical interaction between any of the 4 <jats:italic>SNCA</jats:italic> SNPs and rs1052553 or rs242557, neither on the multiplicative nor on the additive scale.</jats:p></jats:sec><jats:sec><jats:title>Interpretation:</jats:title><jats:p>This study confirms the association between PD and both <jats:italic>SNCA</jats:italic> SNPs and the H1 <jats:italic>MAPT</jats:italic> haplotype. It shows, based on a variety of approaches, that the joint action of variants in these 2 loci is consistent with independent effects of the genes without additional interacting effects. ANN NEUROL 2011</jats:p></jats:sec>