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

• Published in: The Journal of nutrition, health & aging Vol. 13; no. 3; pp. 214 - 219
• Main Authors: Ramírez-Lorca, Reposo, Boada, M., Saez, M. E., Hernandez, I., Mauleon, A., Rosende-Roca, M., Martinez-Lage, P., Gutierrez, M., Real, L. M., Lopez-Arrieta, J., Gayan, J., Antunez, C., Gonzalez-Perez, A., Tarraga, L., Ruiz, A.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Paris Springer-Verlag 01-03-2009; Springer; Springer Nature B.V
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult and adolescent clinical studies; Aged; Aging; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E4 - genetics; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; GAB2 Gene Does Not Modify the Risk of Alzheimer’s Disease in Spanish APOE 4 Carriers; Gene loci; Genetic Markers - genetics; Genetic Predisposition to Disease; Genomes; Genotype & phenotype; Geriatrics/Gerontology; Health risk assessment; Heterozygote; Hospitals; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Neurology; Neurosciences; Nutrition; Odds Ratio; Organic mental disorders. Neuropsychology; Polymorphism, Genetic - genetics; Population-based studies; Primary Care Medicine; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Quality of Life Research; Reverse Transcriptase Polymerase Chain Reaction - methods; Risk Factors; Spain - epidemiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Spain; genetic association studies; APOE; GAB2; Alzheimer’s disease; SNP; Nervous system diseases; Alzheimer disease; Metabolic diseases; Risk; Cerebral disorder; Association; Gene; Central nervous system disease; Risk factor; Genetics; Degenerative disease; Spanish; Carrier; Alzheimer's disease
• ISSN: 1279-7707; 1760-4788
• DOI: 10.1007/s12603-009-0061-6

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 ε4 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 ε4 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 ε4/ ε4 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 single-locus 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 gene-gene 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 ε4 carriers.