MAPT H1 haplotype is associated with late-onset Alzheimer's disease risk in APOE ε 4 noncarriers: Results from the dementia genetics Spanish consortium

Pau Pastor, Fermín Moreno, Jordi Clarimón, Agustín Ruiz, Onofre Combarros, Miguel Calero, Adolfo López De Munain, Maria J. Bullido, Marian M. De Pancorbo, Eva Carro, Anna Antonell, Eliecer Coto, Sara Ortega-Cubero, Isabel Hernandez, Lluís Tárraga, Mercè Boada, Alberto Lleó, Oriol Dols-Icardo, Jaime Kulisevsky, José Luis Vázquez-HigueraJon Infante, Alberto Rábano, Miguel Ángel Fernández-Blázquez, Meritxell Valentí, Begoña Indakoetxea, Myriam Barandiarán, Ana Gorostidi, Ana Frank-García, Isabel Sastre, Elena Lorenzo, María A. Pastor, Xabier Elcoroaristizabal, Martina Lennarz, Wolfang Maier, Alfredo Rámirez, Manuel Serrano-Ríos, Suzee E. Lee, Pascual Sánchez-Juan

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23 Citations (Scopus)

Abstract

© 2016 - IOS Press and the authors. The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR)=2.03; p=0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR=1.12; p=0.0005). Stratification analysis showed that this association was mainly driven by APOE ε4 noncarriers (OR=1.14; p=0.0025). MAPT H1 was also associated with risk for PD (OR=1.30; p=0.0003) and PSP (OR=3.18; p=8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ε4 AD.
Original languageEnglish
Pages (from-to)343-352
JournalJournal of Alzheimer's Disease
Volume49
Issue number2
DOIs
Publication statusPublished - 9 Oct 2015

Keywords

  • A152T
  • Alzheimer's disease
  • frontotemporal dementia
  • genetic association
  • H1H2
  • MAPT

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