Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study

被引：31

作者：

Cuyvers, Elise ^{[1
,2
,3
]}

van der Zee, Julie ^{[1
,2
,3
]}

Bettens, Karolien ^{[1
,2
,3
]}

Engelborghs, Sebastiaan ^{[2
,3
,4
,5
]}

Vandenbulcke, Mathieu ^{[6
,7
,8
]}

Robberecht, Caroline ^{[1
,2
,3
]}

Dillen, Lubina ^{[1
,2
,3
]}

Merlin, Celine ^{[1
,2
,3
]}

Geerts, Nathalie ^{[1
,2
,3
]}

Graff, Caroline ^{[9
,10
]}

Thonberg, Hakan ^{[9
,10
]}

Chiang, Huei-Hsin ^{[9
]}

Pastor, Pau ^{[11
,12
,13
]}

Ortega-Cubero, Sara ^{[11
,13
]}

Pastor, Maria A. ^{[13
,14
,15
]}

Diehl-Schmid, Janine ^{[16
]}

Alexopoulos, Panagiotis ^{[16
]}

Benussi, Luisa ^{[17
]}

Ghidoni, Roberta ^{[17
]}

Binetti, Giuliano ^{[17
]}

Nacmias, Benedetta ^{[18
]}

Sorbi, Sandro ^{[18
]}

Sanchez-Valle, Raquel ^{[19
]}

Llado, Albert ^{[19
]}

Gelpi, Ellen ^{[20
]}

Almeida, Maria Rosario ^{[21
]}

Santana, Isabel ^{[21
]}

Clarimon, Jordi ^{[13
,22
]}

Lleo, Alberto ^{[13
,22
]}

Fortea, Juan ^{[13
,22
]}

de Mendonca, Alexandre ^{[23
,24
]}

Martins, Madalena ^{[23
,24
]}

Borroni, Barbara ^{[25
]}

Padovani, Alessandro ^{[25
]}

Matej, Radoslav ^{[26
,27
]}

Rohan, Zdenek ^{[26
,27
,28
]}

Ruiz, Agustin ^{[29
]}

Frisoni, Giovanni B. ^{[30
,31
,32
,33
]}

Fabrizi, Gian Maria ^{[34
]}

Vandenberghe, Rik ^{[8
,35
]}

De Deyn, Peter P. ^{[2
,3
,4
,5
,36
,37
]}

Van Broeckhoven, Christine ^{[1
,2
,3
]}

Sleegers, Kristel ^{[1
,2
,3
]}

机构：

[1] VIB, Dept Mol Genet, Antwerp, Belgium

[2] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium

[3] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, B-2020 Antwerp, Belgium

[4] Hosp Network Antwerp Middelheim & Hoge Beuken, Dept Neurol, Antwerp, Belgium

[5] Hosp Network Antwerp Middelheim & Hoge Beuken, Memory Clin, Antwerp, Belgium

[6] Univ Leuven, Dept Old Age Psychiat, Leuven, Belgium

[7] Univ Leuven, Memory Clin, Leuven, Belgium

[8] Univ Hosp Leuven Gasthuisberg, Leuven, Belgium

[9] Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden

[10] Karolinska Univ Hosp, Genet Unit, Dept Geriatr Med, Stockholm, Sweden

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

[12] Hosp Univ Mutua Terrassa, Dept Neurol, Barcelona, Spain

[13] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

[14] Univ Navarra, Ctr Appl Med Res CIMA, Div Neurosci, Neuroimaging Lab, E-31080 Pamplona, Spain

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

[16] Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany

[17] Ist Ctr San Giovanni Dio Fatebenefratelli, IRCCS, Mol Markers Lab, Brescia, Italy

[18] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy

[19] Hosp Clin Barcelona, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain

[20] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Neurol Tissue Bank Biobanc, Barcelona, Spain

[21] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal

[22] Univ Autonoma Barcelona, Dept Neurol, IIB St Pau, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain

[23] Univ Lisbon, Fac Med, P-1699 Lisbon, Portugal

[24] Univ Lisbon, Inst Mol Med, P-1699 Lisbon, Portugal

[25] Univ Brescia, Neurol Unit, Brescia, Italy

[26] Charles Univ Prague, Fac Med 1, Dept Neurol, Ctr Clin Neurosci, Prague, Czech Republic

[27] Thomayer Hosp, Dept Pathol & Mol Med, Prague, Czech Republic

[28] Charles Univ Prague, Med Fac 3, Inst Pathol, Prague, Czech Republic

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

[30] Hop Cantonal Univ Geneva, Dept Med Interne Rehabil & Geriatrie, Geneva, Switzerland

[31] Hop Cantonal Univ Geneva, Dept Sante Mentale & Psychiat, Geneva, Switzerland

[32] Univ Geneva, Geneva, Switzerland

[33] IRCCS Fatebenefratelli, Alzheimers Neuroimaging & Epidemiol Lab, Brescia, Italy

[34] Univ Verona, Univ Hosp GB Rossi, Neurol Sect, Dept Neurol & Movements Sci, I-37100 Verona, Italy

[35] Univ Leuven, Dept Neurol, Lab Cognit Neurol, Leuven, Belgium

[36] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, Groningen, Netherlands

[37] Univ Groningen, Univ Med Ctr Groningen, Alzheimer Res Ctr, Groningen, Netherlands

来源：

NEUROBIOLOGY OF AGING | 2015年 / 36卷 / 05期

基金：

瑞典研究理事会;

关键词：

SQSTM1/p62; Alzheimer's disease; Rare variants; Meta-analysis; European early-onset dementia consortium; PAGETS-DISEASE; FRONTOTEMPORAL DEMENTIA; NATIONAL INSTITUTE; SEQUESTOSOME; 1/P62; MUTATIONS; BONE; P62; SUSCEPTIBILITY; PATHOGENESIS; INCLUSIONS;

D O I：

10.1016/j.neurobiolaging.2015.02.014

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：

Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European earlyonset dementia cohorts (926 early-onset Alzheimer's disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292- and p.R312- showed nominal association with AD (odds ratio(p.D292=) - 1.11 [95% confidence interval = 1-1.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD. (C) 2015 The Authors. Published by Elsevier Inc.

引用

页码：2005.e15 / 2005.e22

页数：8

共 32 条

[1] Follow-Up Study of Susceptibility Loci for Alzheimer's Disease and Onset Age Identified by Genome-Wide Association
Bettens, Karolien
Brouwers, Nathalie
Van Miegroet, Helen
Gil, Ana
Engelborghs, Sebastiaan
De Deyn, Peter P.
Vandenberghe, Rik
Van Broeckhoven, Christine
Sleegers, Kristel
[J]. JOURNAL OF ALZHEIMERS DISEASE, 2010, 19 (04) : 1169 - 1175
[2] p62/SQSTM1 - A missing link between protein aggregates and the autophagy machinery
Bjorkoy, Geir
Lamark, Trond
Johansen, Terje
[J]. AUTOPHAGY, 2006, 2 (02) : 138 - 139
[3] Paget's disease of bone in the French population:: Novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations
Collet, Corinne
Michou, Laetitia
Audran, Maurice
Chasseigneaux, Stephanie
Hilliquin, Pascal
Bardin, Thomas
Lemaire, Isabelle
Cornelis, Francois
Launay, Jean-Marie
Orcel, Philippe
Laplanche, Jean-Louis
[J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (02) : 310 - 317
[4] Dose dependent effect of APOE ε4 on behavioral symptoms in frontal lobe dementia
Engelborghs, S
Dermaut, B
Mariën, P
Symons, A
Vloeberghs, E
Maertens, K
Somers, N
Goeman, J
Rademakers, R
Van den Broeck, M
Pickut, B
Cruts, M
Van Broeckhoven, C
De Deyn, PP
[J]. NEUROBIOLOGY OF AGING, 2006, 27 (02) : 285 - 292
[5] Prospective Belgian study of neurodegenerative and vascular dementia:: APOE genotype effects
Engelborghs, S
Dermaut, B
Goeman, J
Saerens, J
Mariën, P
Pickut, BA
Van den Broeck, M
Serneels, S
Cruts, M
Van Broeckhoven, C
De Deyn, PP
[J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2003, 74 (08) : 1148 - 1151
[6] SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Fecto, Faisal
Yan, Jianhua
Vemula, S. Pavan
Liu, Erdong
Yang, Yi
Chen, Wenjie
Zheng, Jian Guo
Shi, Yong
Siddique, Nailah
Arrat, Hasan
Donkervoort, Sandra
Ajroud-Driss, Senda
Sufit, Robert L.
Heller, Scott L.
Deng, Han-Xiang
Siddique, Teepu
[J]. ARCHIVES OF NEUROLOGY, 2011, 68 (11) : 1440 - 1446
[7] MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN
FOLSTEIN, MF
FOLSTEIN, SE
MCHUGH, PR
[J]. JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) : 189 - 198
[8] Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis
Hirano, Makito
Nakamura, Yusaku
Saigoh, Kazumasa
Sakamoto, Hikaru
Ueno, Shuichi
Isono, Chiharu
Miyamoto, Katsuichi
Akamatsu, Maiko
Mitsui, Yoshiyuki
Kusunoki, Susumu
[J]. NEUROLOGY, 2013, 80 (05) : 458 - 463
[9] Three novel mutations in SQSTM1 identified in familial Paget's disease of bone
Johnson-Pais, TL
Wisdom, JH
Weldon, KS
Cody, JD
Hansen, MF
Singer, FR
Leach, RJ
[J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2003, 18 (10) : 1748 - 1753
[10] VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: Review of a unique disorder
Kimonis, Virginia E.
Fulchiero, Erin
Vesa, Jouni
Watts, Giles
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2008, 1782 (12): : 744 - 748

← 1 2 3 4 →