Association study of the GAB2 gene with the risk of developing Alzheimer's disease.
The first genome-wide association in Alzheimer's disease (AD) suggested that the GAB2 gene rs2373115 polymorphism may be a strong risk factor in APOE varepsilon4-carriers. We failed to detect an association of rs2373115 with the risk of developing AD in three populations (totalling 1406 controls and 1749 AD cases) whatever the APOE status, even if we observed a slight tendency for an increase of the GG genotype (OR (GG versus GT+TT)=1.3, 95% CI 1.0-1.6, p=0.09) and the G allele frequency (OR=1.3, 95%CI 1.0-1.6, p=0.05) in varepsilon4-carriers. In addition, the rs2373115 did not modulate the extent of tau phosphorylation in the brain of 89 AD cases. The GAB2 gene is at best a minor genetic determinant of AD.
Chapuis
Julien
J
INSERM,U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Hannequin
Didier
D
Pasquier
Florence
F
Bentham
Peter
P
Brice
Alexis
A
Leber
Isabelle
I
Frebourg
Thierry
T
Deleuze
Jean-François
JF
Cousin
Emmanuelle
E
Thaker
Uma
U
Amouyel
Philippe
P
Mann
David
D
Lendon
Corinne
C
Campion
Dominique
D
Lambert
Jean-Charles
JC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003431:Cross-Cultural Comparison; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk
D048868:Adaptor Proteins, Signal Transducing; D053327:Apolipoprotein E4; C490895:GAB2 protein, human