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MAPT H1 haplotype is associated with late-onset Alzheimer's disease risk in APOE e4 noncarriers: results from the Dementia Genetics Spanish Consortium

Autores: Pastor Muñoz, Pau; Moreno, F.; Clarimón, J.; Ruiz, A.; Combarros, O.; Calero, Miguel; López de Munain, A.; Bullido, M. J.; de Pancorbo, M. M.; Carro, E.; Antonell, A.; Coto, E.; Ortega Cubero, Sara; Hernandez, I,; Tárraga, L.; Boada, M.; Lleó, A.; Dols-Icardo, O.; Kulisevsky, J.; Vázquez-Higuera, J. L.; Infante, J.; Rábano, A.; Fernández-Blázquez, M. Á.; Valentí, M.; Indakoetxea, B.; Barandiarán, M.; Gorostidi, A.; Frank-García, A.; Sastre, I.; Lorenzo Ramos, María Elena; Pastor, María A.; Elcoroaristizabal, X.; Lennarz, M.; Maier, W.; Rámirez, A.; Serrano-Ríos, M.; Lee, S. E.; Sánchez-Juan, P.
ISSN: 1387-2877
Volumen: 49
Número: 2
Páginas: 343 - 352
Fecha de publicación: 2015
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 ¿4 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 ¿4 AD.