TY - JOUR
T1 - Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia
AU - Ruiz, Agustín
AU - Dols-Icardo, Oriol
AU - Bullido, María J.
AU - Pastor, Pau
AU - Rodríguez-Rodríguez, Eloy
AU - López de Munain, Adolfo
AU - de Pancorbo, Marian M.
AU - Pérez-Tur, Jordi
AU - Álvarez, Victoria
AU - Antonell, Anna
AU - López-Arrieta, Jesús
AU - Hernández, Isabel
AU - Tárraga, Lluís
AU - Boada, Mercè
AU - Lleó, Alberto
AU - Blesa, Rafael
AU - Frank-García, Ana
AU - Sastre, Isabel
AU - Razquin, Cristina
AU - Ortega-Cubero, Sara
AU - Lorenzo, Elena
AU - Sánchez-Juan, Pascual
AU - Combarros, Onofre
AU - Moreno, Fermín
AU - Gorostidi, Ana
AU - Elcoroaristizabal, Xabier
AU - Baquero, Miquel
AU - Coto, Eliecer
AU - Sánchez-Valle, Raquel
AU - Clarimón, Jordi
PY - 2014/1/1
Y1 - 2014/1/1
N2 - A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR]= 4.12, 95% confidence interval [CI]= 1.21-14.00, p= 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR= 4.11, 95% CI= 2.99-5.68, p= 5.27×10-18). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD. © 2014 Elsevier Inc.
AB - A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR]= 4.12, 95% confidence interval [CI]= 1.21-14.00, p= 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR= 4.11, 95% CI= 2.99-5.68, p= 5.27×10-18). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD. © 2014 Elsevier Inc.
KW - Alzheimer's disease
KW - Frontotemporal dementia
KW - Genetic association
KW - P.R47H
KW - Rare variant
KW - TREM2
U2 - 10.1016/j.neurobiolaging.2013.08.011
DO - 10.1016/j.neurobiolaging.2013.08.011
M3 - Article
SN - 0197-4580
VL - 35
SP - 444.e1-444.e4
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 2
ER -