Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.
PLoS Genet
; 12(10): e1006327, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27764101
ABSTRACT
We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the ß-amyloid cascade.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tropomiosina
/
Proteínas de Drosophila
/
Receptores Notch
/
Enfermedad de Alzheimer
/
Proteínas de la Membrana
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Animals
/
Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Islandia