The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease: a Meta-Analysis Study

被引：50

作者：

Lambert, Jean-Charles ^{[1
,2
]}

Sleegers, Kristel ^{[3
]}

Gonzalez-Perez, Antonio ^{[6
]}

Ingelsson, Martin ^{[7
]}

Beecham, Gary W. ^{[8
]}

Hiltunen, Mikko ^{[9
,10
]}

Combarros, Onofre ^{[11
,12
]}

Bullido, Maria J. ^{[13
,14
]}

Brouwers, Nathalie ^{[3
,4
,5
]}

Bettens, Karolien ^{[3
,4
,5
]}

Berr, Claudine ^{[15
]}

Pasquier, Florence ^{[2
,16
]}

Richard, Florence ^{[1
,2
,16
]}

DeKosky, Steven T. ^{[17
]}

Hannequin, Didier ^{[18
]}

Haines, Jonathan L. ^{[19
]}

Tognoni, Gloria ^{[20
]}

Fievet, Nathalie ^{[1
]}

Dartigues, Jean-Francois ^{[21
]}

Tzourio, Christophe ^{[22
,23
]}

Engelborghs, Sebastiaan ^{[24
,25
]}

Arosio, Beatrice ^{[26
]}

Coto, Elicer ^{[27
]}

De Deyn, Peter ^{[4
,5
,24
,25
]}

Del Zompo, Maria ^{[28
]}

Mateo, Ignacio ^{[11
,12
]}

Boada, Merce ^{[29
,30
]}

Antunez, Carmen ^{[31
,32
]}

Lopez-Arrieta, Jesus ^{[33
]}

Epelbaum, Jacques ^{[34
]}

Schjcide, Brit-Marcn Michaud ^{[35
]}

Frank-Garcia, Ana ^{[36
,37
]}

Gicdraitis, Vilmentas ^{[7
]}

Helisalmi, Seppo ^{[11
,12
]}

Porcellini, Elisa ^{[38
]}

Pilotto, Alberto ^{[39
]}

Forti, Paola ^{[40
]}

Ferri, Raffaele ^{[41
]}

Delepine, Marc ^{[42
]}

Zelenika, Diana ^{[42
]}

Lathrop, Mark ^{[42
,43
]}

Scarpini, Elio ^{[44
]}

Siciliano, Gabriele ^{[20
]}

Solfrizzi, Vincenzo ^{[45
]}

Sorbi, Sandro ^{[18
,46
]}

Spalletta, Gianfranco ^{[47
]}

Ravaglia, Giovanni

Valdivieso, Fernando ^{[14
]}

Vepsalainen, Saila ^{[7
]}

Alvarez, Victoria

机构：

[1] Inst Pasteur, Unite INSERM 744, BP 245,1 Rue,Professeur Calmette, F-59019 Lille, France

[2] Univ Lille Nord France, Lille, France

[3] Dept Mol Genet VIB, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[4] Univ Antwerp, B-2020 Antwerp, Belgium

[5] Inst Born Bunge, Antwerp, Belgium

[6] Dept Struct Genom, Seville, Spain

[7] Uppsala Univ, Stockholm, Sweden

[8] Univ Miami, Sch Med, John P Hussman Inst Human Gen, Miami, FL USA

[9] Univ Hosp, Kuopio, Finland

[10] Univ Kuopio, Dept Neurol, Kuopio, Finland

[11] Univ Cantabria, Marques Valdecilla Univ Hosp, Neurol Serv, Santander, Spain

[12] Univ Cantabria, CIBERNED, Santander, Spain

[13] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa UAM CSIC, Madrid, Spain

[14] Univ Autonoma Madrid, CIBERNED, Madrid, Spain

[15] Hop Colombiere, INSERM U888, Montpellier, France

[16] CHRU Lille, Lille, France

[17] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA

[18] Fac Med Pharmacie Rouen, INSERM U614, Rouen, France

[19] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Human Genet Res, Nashville, TN USA

[20] Univ Pisa, Dept Neurosci, Neurol Clin, Pisa, Italy

[21] Victor Segalen Univ, INSERM U897, Bordeaux, France

[22] INSERM U708, Paris, France

[23] UPMC Univ Paris 06, Paris, France

[24] ZNA Middelheim, Memory Clin, Antwerp, Belgium

[25] ZNA Middelheim, Dept Neurol, Antwerp, Belgium

[26] Fdn Policlin IRCCS, Dept Internal Med, Milan, Italy

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

[28] Univ Cagliari, Dept Neurosci, Clin Pharmacol Sect, Cagliari, Italy

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

[30] Hosp G Univ Vall Hebron, Dept Neurol, Barcelona, Spain

[31] Alzheimur Fdn, Murcia, Spain

[32] Univ Hosp Virgen Arrixaca, Dementia Unit, Murcia, Spain

[33] Univ Hosp Paz Cantoblanco, Memory Unit, Madrid, Spain

[34] Univ Paris 05, UMR 894, INSERM Fac Med, Paris, France

[35] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Gen, Berlin, Germany

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

[37] CIBERNED, Madrid, Spain

[38] Univ Bologna, Sch Med, Dept Expt Pathol, Bologna, Italy

[39] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit & Gerontol Geriatr Res Lab, San Giovanni Rotondo, Italy

[40] Univ Hosp S Orsola Malpighi, Dept Internal Med Cardiol & Hepatol, Bologna, Italy

[41] IRCCS Oasi Maria SS, Troina, Italy

[42] Inst Genom, Commissariat Energie Atom, Ctr Natl Genotypage, Evry, France

[43] Fdn Jean Dausset CEPH, Paris, France

[44] Univ Milan, Dept Neurol Sci, Dino Ferrari Ctr, IRCCS Osped Maggiore Policlin, Milan, Italy

[45] Univ Bari, Dept Geriatr, Ctr Aging Brain, Memory Unit, Bari, Italy

[46] Dept Neurol & Psychiat Sci, Florence, Italy

[47] IRCCS Santa Lucia Fdn, Dept Clin & Behav Neurol, Rome, Italy

[48] Univ Milano Bicocca, Dept Clin Med & Prevent, Monza, Italy

[49] Univ Manchester, Greater Manchester Neurosci Ctr, Manchester, Lancs, England

[50] N Shore LIJ, Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY USA

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2010年 / 22卷 / 01期

基金：

芬兰科学院;

关键词：

Age at onset; Alzheimer's disease; apolipoprotein E; CALHM1; polymorphism; GENOME-WIDE ASSOCIATION; S-TRANSFERASE OMEGA-1; NO ASSOCIATION; AT-ONSET; POPULATION-STRUCTURE; IDENTIFIES VARIANTS; RISK; HETEROGENEITY; HOMEOSTASIS; DEMENTIA;

D O I：

10.3233/JAD-2010-100933

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.

引用

页码：247 / 255

页数：9

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