Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

被引：90

作者：

Ruiz, Agustin ^{[1
,2
]}

Dols-Icardo, Oriol ^{[3
,4
]}

Bullido, Maria J. ^{[4
,5
,6
]}

Pastor, Pau ^{[4
,7
,8
]}

Rodriguez-Rodriguez, Eloy ^{[4
,9
,10
]}

Lopez de Munain, Adolfo ^{[4
,11
,12
]}

de Pancorbo, Marian M. ^{[13
]}

Perez-Tur, Jordi ^{[4
,14
]}

Alvarez, Victoria ^{[15
]}

Antonell, Anna ^{[16
]}

Lopez-Arrieta, Jesus ^{[6
,17
]}

Hernandez, Isabel ^{[1
,2
]}

Tarraga, Lluis ^{[1
,2
]}

Boada, Merce ^{[1
,2
,18
]}

Lleo, Alberto ^{[3
,4
]}

Blesa, Rafael ^{[3
,4
]}

Frank-Garcia, Ana ^{[4
,6
,19
]}

Sastre, Isabel ^{[4
,5
,6
]}

Razquin, Cristina ^{[4
,7
]}

Ortega-Cubero, Sara ^{[4
,7
,8
]}

Lorenzo, Elena ^{[4
,7
]}

Sanchez-Juan, Pascual ^{[4
,9
,10
]}

Combarros, Onofre ^{[4
,9
,10
]}

Moreno, Fermin ^{[4
,11
,12
]}

Gorostidi, Ana ^{[4
,11
,12
]}

Elcoroaristizabal, Xabier ^{[13
]}

Baquero, Miquel ^{[20
,21
]}

Coto, Eliecer ^{[15
]}

Sanchez-Valle, Raquel ^{[16
]}

Clarimon, Jordi ^{[3
,4
]}

机构：

[1] Inst Catala Neurociencies Aplicades, Fundacio ACE, Alzheimer Res Ctr, Barcelona, Spain

[2] Inst Catala Neurociencies Aplicades, Fundacio ACE, Memory Clin, Barcelona, Spain

[3] Univ Autonoma Barcelona, Hosp Sant Pau, Sant Pau Biomed Res Inst, Memory Unit,Dept Neurol, E-08193 Barcelona, Spain

[4] Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain

[5] Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid, Spain

[6] Hosp la Paz IdIPaz, Inst Sanit Res, Madrid, Spain

[7] Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain

[8] Univ Navarra, Sch Med, Clin Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain

[9] Univ Cantabria, Univ Hosp Marques de Valdecilla, Neurol Serv, E-39005 Santander, Spain

[10] IFIMAV, Univ Hosp Marques de Valdecilla, Neurol Serv, Santander, Spain

[11] Univ Basque Contry EHU UPV, Inst Biodonostia, Neurosci Area, San Sebastian, Spain

[12] Univ Basque Contry EHU UPV, Dept Neurosci, San Sebastian, Spain

[13] Univ Pais Vasco UPV EHU, Ctr Invest Lascaray Ikergunea, BIOMICs Res Grp, Vitoria, Spain

[14] CSIC, Inst Biomed Valenciae, Valencia, Spain

[15] Hosp Univ Cent Asturias, Mol Genet Lab, Genet Unit, Oviedo, Spain

[16] IDIBAPS, Hosp Clin, Dept Neurol, Barcelona, Spain

[17] Univ Hosp La Paz Cantoblanco, Memory Unit, Madrid, Spain

[18] Univ Autonoma Barcelona VHIR UAB, Inst Recerca, Hosp Univ Vall dHebron, Barcelona, Spain

[19] Hosp Univ La Paz UAM, Neurol Serv, Madrid, Spain

[20] Hosp Univ La Fe, Neurol Serv, Valencia, Spain

[21] Politecn La Fe, Valencia, Spain

来源：

NEUROBIOLOGY OF AGING | 2014年 / 35卷 / 02期

关键词：

Alzheimer's disease; Frontotemporal dementia; TREM2; Genetic association; p.R47H; Rare variant; MUTATIONS;

D O I：

10.1016/j.neurobiolaging.2013.08.011

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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 x 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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：444.e1 / 444.e4

页数：4

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