Conflicting reports of possible small increase in Alzheimer's risk. Currently dubious at best.
rs2373115 is one of several SNPs in the GAB2 gene indicating an increased risk (OR 4.1) of late-onset Alzheimer's disease, but apparently only in individuals also carrying ApoE4 alleles, i.e. rs429358(C) alleles [PMID 17553421]
[PMID 19262956] rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE e4 carriers.
rs2373115(G) is the risk allele.
[PMID 17553421] (p = 9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81-14.69)
However, a separate study of 1,749 Alzheimer patients concluded that this GAB2 SNP is "at best a minor genetic determinant" since the authors of this study observed only a slight tendency for an increase of the (G;G) genotype (odds ratio of 1.3 vs (G;T) and (T;T), CI:1.0-1.6, p=0.09) and for an increase in the G allele frequency (odds ratio 1.3, CI:1.0-1.6, p=0.05) in ApoE4-carriers.[PMID 18272374]
[PMID 19118819] A new (Dec 2008) meta-analysis concludes that, yes, indeed, rs2373115 is associated with increased risk for Alzheimer's disease among ApoE4 carriers, with an odds ratio of 1.58 (CI: 1.17 - 2.14, p = 3 x 10e-3), but only among carriers. This meta-analysis pooled published studies with a new study of 443 AD cases.
[PMID 19276544] A study of 579 Italian Alzheimer's patients saw this association, but only in ApoE4 non-carriers, suggesting it might be an independent risk factor for the disease.
|Condition||APOE*e4 carriers with late onset Alzheimer's disease|
[PMID 21285854] Association Study of the GAB2 Gene With the Risk of Alzheimer Disease in the Chinese Population
[PMID 19204163] GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
[PMID 19924507] GAB2 is not associated with late-onset Alzheimer's disease in Chinese Han.
[PMID 20061627] Genome-wide scan of copy number variation in late-onset Alzheimer's disease.
[PMID 20188796] Association analysis between polymorphism rs2373115 of gene GRB-associated binding protein 2 and Mongolian Alzheimer patients.
[PMID 20574532] Intermediate phenotypes identify divergent pathways to Alzheimer's disease.
[PMID 24161894] GAB2 polymorphism rs2373115 confers susceptibility to sporadic Alzheimer's disease
[PMID 23525328] Single-nucleotide polymorphisms of GSK3B, GAB2 and SORL1 in late-onset Alzheimer's disease: interactions with the APOE genotype
[PMID 26611835] Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1.