GAB2 polymorphism rs2373115 confers susceptibility to sporadic Alzheimer's disease

Abstract

It has been reported that a single nucleotide polymorphism (SNP), rs2373115, in the GRB-associated binding protein 2 (GAB2) gene was associated with late-onset AD in Caucasians. Subsequently, other researchers have attempted to validate this finding in different ethnic populations. However, these findings have produced both negative and positive results. To derive a more precise estimation for whether GAB2 polymorphism rs2373115 is associated with sporadic Alzheimer's disease (SAD), we performed the present meta-analysis. Databases including PubMed, AlzGene, China National Knowledge Infrastructure (CNKI) and Wan Fang were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. All analyses were calculated using STATA Version 11.0 and RevMan (v.5.1) software. Ten total case-control studies were included. The statistical results showed that GAB2 SNP rs2373115 is significantly associated with an increased risk for SAD, and the subgroup analysis showed that SNP rs2373115 may only be associated with an increased risk for SAD risk in Caucasians but not in Asians. Furthermore, in APOE ɛ4 carriers or noncarriers, those with rs2373115 genotype GG did not have a significantly higher risk for SAD compared with those with genotype GT and TT (APOE ɛ4 carriers: OR=1.20, 95% CI=0.92-1.56, P=0.178; APOE ɛ4 noncarriers: OR=1.08, 95% CI=0.97-1.20, P=0.157) in the present study. The current meta-analysis further supports previous findings that the GAB2 gene may be associated with SAD risk.

Keywords: AD; APOE; APP; Allele; Alzheimer's disease; CI; CNKI; China National Knowledge Infrastructure; DSM; Diagnostic and Statistical Manual of Mental Disorders; FAD; GAB2; GRB-associated binding protein 2 gene; HRMA; HWE; Hardy–Weinberg equilibrium; NINCDS-ADRDA; National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's disease and Related Disorders Association; OR; OR(G); PCR; PSEN 1; PSEN 2; RFLP; SAD; SNP; Single nucleotide polymorphism; amyloid precursor protein; apolipoprotein E; confidence interval; familial Alzheimer's disease; generalized odds ratio; high resolution melting analysis; odds ratio; polymerase chain reaction; presenilin 1; presenilin 2; restriction fragment length polymorphism; single nucleotide polymorphism; sporadic Alzheimer's disease.