GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers.
OBJECTIVE
The genetic basis of Alzheimer's disease (AD) is being analyzed in multiple whole genome association studies (WGAS). The GAB2 gene has been proposed as a modifying factor of APOE epsilon 4 allele in a recent case-control WGAS conducted in the US. Given the potential application of these novel results in AD diagnostics, we decided to make an independent replication to examine the GAB2 gene effect in our series.


METHODS
We are conducting a multicenter population-based study of AD in Spain.


METHODS
We analyzed a total of 1116 Spanish individuals. Specifically, 521 AD patients, 475 controls from the general population and 120 neurologically-normal elderly controls (NNE controls).


METHODS
We have genotyped GAB2 (rs2373115 G/T) and APOE rs429358 (SNP112)/rs7412 (SNP158) polymorphisms using real time-PCR technologies.


RESULTS
As previously reported in Spain, APOE epsilon 4 allele was strongly associated with AD in our series (OR=2.88 [95% C.I. 2.16- 3.84], p=7.38E-11). Moreover, a large effect for epsilone 4/epsilone 4 genotype was also observed (OR=14.45 [95% C.I., 3.34-125.2], p=1.8E-6). No difference between the general population and the NNE controls series were observed for APOE genotypes (P > 0.61). Next, we explored GAB2 rs2373115 SNP singlelocus association using different genetic models and comparing AD versus controls or NNE controls. No evidence of association with AD was observed for this GAB2 marker (p > 0.17). To evaluate GAB2-APOE genegene interactions, we stratified our series according to APOE genotype and case-control status, in accordance with the original studies. Again, no evidence of genetic association with AD was observed in any strata of GAB2-APOE loci pair (p > 0.34).


CONCLUSIONS
GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.
Ramirez-Lorca
R
R
Department of Structural Genomics, NeoCodex, Sevilla, Spain.
Boada
M
M
Saez
M E
ME
Hernandez
I
I
Mauleon
A
A
Rosende-Roca
M
M
Martinez-Lage
P
P
Gutierrez
M
M
Real
L M
LM
Lopez-Arrieta
J
J
Gayan
J
J
Antunez
C
C
Gonzalez-Perez
A
A
Tarraga
L
L
Ruiz
A
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
D048868:Adaptor Proteins, Signal Transducing; D053327:Apolipoprotein E4; C490895:GAB2 protein, human; D005819:Genetic Markers