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.
|qualified_impact||Insufficiently evaluated pathogenic|
[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.