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Multicenter Study
. 2009 Mar;13(3):214-9.
doi: 10.1007/s12603-009-0061-6.

GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers

R Ramirez-Lorca  1 , M Boada, M E Saez, I Hernandez, A Mauleon, M Rosende-Roca, P Martinez-Lage, M Gutierrez, L M Real, J Lopez-Arrieta, J Gayan, C Antunez, A Gonzalez-Perez, L Tarraga, A Ruiz
Affiliations
Multicenter Study

GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers

R Ramirez-Lorca et al. J Nutr Health Aging. 2009 Mar.

Abstract

Objectives: 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.

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

Participants: 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).

Conclusion: GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.

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Figures

Supplementary Figure 1
Supplementary Figure 1
Linkage Disequilibrium Structure for the region involving GAB2 gene in Spanish Population
See this image and copyright information in PMC

References

    1. Evans D.A., Beckett L.A., Field T.S., et al. Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons. Jama. 1997;277:822–824. 10.1001/jama.277.10.822 PubMed PMID: 9052713. - DOI - PubMed
    1. Parihar M.S., Hemnani T. Alzheimer's disease pathogenesis and therapeutic interventions. J Clin Neurosci. 2004;11:456–467. 10.1016/j.jocn.2003.12.007 PubMed PMID: 15177383. - DOI - PubMed
    1. Crutcher K.A. Apolipoprotein E is a prime suspect, not just an accomplice, in Alzheimer's disease. J Mol Neurosci. 2004;23:181–188. 10.1385/JMN:23:3:181 PubMed PMID: 15181246. - DOI - PubMed
    1. Bertram L., McQueen M.B., Mullin K., et al. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nature genetics. 2007;39:17–23. 10.1038/ng1934 PubMed PMID: 17192785. - DOI - PubMed
    1. Corbo R.M., Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty' allele? Annals of human genetics. 1999;63:301–310. 10.1046/j.1469-1809.1999.6340301.x PubMed PMID: 10738542. - DOI - PubMed

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