The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.
The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 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 ε4 allele of the APOE gene.
Lambert
Jean-Charles
JC
Unité INSERM 744, Institut Pasteur de Lille BP 245,1, rue du professeur Calmette, F59019Lille cedex, France. jeancharles.lambert@pasteurlille.fr
Sleegers
Kristel
K
González-Pérez
Antonio
A
Ingelsson
Martin
M
Beecham
Gary W
GW
Hiltunen
Mikko
M
Combarros
Onofre
O
Bullido
Maria J
MJ
Brouwers
Nathalie
N
Bettens
Karolien
K
Berr
Claudine
C
Pasquier
Florence
F
Richard
Florence
F
Dekosky
Steven T
ST
Hannequin
Didier
D
Haines
Jonathan L
JL
Tognoni
Gloria
G
Fiévet
Nathalie
N
Dartigues
Jean-François
JF
Tzourio
Christophe
C
Engelborghs
Sebastiaan
S
Arosio
Beatrice
B
Coto
Elicer
E
De Deyn
Peter
P
Del Zompo
Maria
M
Mateo
Ignacio
I
Boada
Merce
M
Antunez
Carmen
C
Lopez-Arrieta
Jesus
J
Epelbaum
Jacques
J
Schjeide
Brit-Maren Michaud
BM
Frank-Garcia
Ana
A
Giedraitis
Vilmentas
V
Helisalmi
Seppo
S
Porcellini
Elisa
E
Pilotto
Alberto
A
Forti
Paola
P
Ferri
Raffaele
R
Delepine
Marc
M
Zelenika
Diana
D
Lathrop
Mark
M
Scarpini
Elio
E
Siciliano
Gabriele
G
Solfrizzi
Vincenzo
V
Sorbi
Sandro
S
Spalletta
Gianfranco
G
Ravaglia
Giovanni
G
Valdivieso
Fernando
F
Vepsäläinen
Saila
S
Alvarez
Victoria
V
Bosco
Paolo
P
Mancuso
Michelangelo
M
Panza
Francesco
F
Nacmias
Benedetta
B
Bossù
Paola
P
Hanon
Olivier
O
Piccardi
Paola
P
Annoni
Giorgio
G
Mann
David
D
Marambaud
Philippe
P
Seripa
Davide
D
Galimberti
Daniela
D
Tanzi
Rudolph E
RE
Bertram
Lars
L
Lendon
Corinne
C
Lannfelt
Lars
L
Licastro
Federico
F
Campion
Dominique
D
Pericak-Vance
Margaret A
MA
Soininen
Hilkka
H
Van Broeckhoven
Christine
C
Alpérovitch
Annick
A
Ruiz
Agustin
A
Kamboh
M Ilyas
MI
Amouyel
Philippe
P
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
D053327:Apolipoprotein E4; C530077:CALHM1 protein, human; D015220:Calcium Channels; D008562:Membrane Glycoproteins