GAB2 is not associated with late-onset Alzheimer's disease in Japanese.

Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
European journal of human genetics: EJHG (Impact Factor: 3.56). 11/2008; 17(5):682-6. DOI: 10.1038/ejhg.2008.181
Source: PubMed

ABSTRACT The varepsilon4 allele of the apolipoprotein E gene (APOE) is unequivocally recognized as a genetic risk factor for late-onset Alzheimer's disease (LOAD). Recently, single-nucleotide polymorphisms (SNPs) of the GRB2-associated binding protein 2 gene (GAB2) were shown to be associated with LOAD in Caucasians carrying the APOE-varepsilon4 allele through a genome-wide association study. Here, we attempted to replicate the finding by genotyping these SNPs in a large clinical cohort of Japanese. We observed no association of any of the SNPs with LOAD. GAB2 may not be a disease susceptibility gene for LOAD in Japanese.

  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been reported that a single nucleotide polymorphism (SNP), rs2373115, in the GRB-associated binding protein 2 gene (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.
    Neuroscience Letters 10/2013; · 2.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GRB-associated binding protein 2 (GAB2) represents a compelling genome-wide association signal for late-onset Alzheimer's disease (LOAD) with reported odds ratios (ORs) ranging from 0.75-0.85. We tested eight GAB2 variants in four North American Caucasian case-control series (2,316 LOAD, 2,538 controls) for association with LOAD. Meta-analyses revealed ORs ranging from (0.61-1.20) with no significant association (all p>0.32). Four variants were hetergeneous across the populations (all p<0.02) due to a potentially inflated effect size (OR = 0.61-0.66) only observed in the smallest series (702 LOAD, 209 controls). Despite the lack of association in our series, the previously reported protective association for GAB2 remained after meta-analyses of our data with all available previously published series (11,952-22,253 samples; OR = 0.82-0.88; all p<0.04). Using a freely available database of lymphoblastoid cell lines we found that protective GAB2 variants were associated with increased GAB2 expression (p = 9.5×10(-7)-9.3×10(-6)). We next measured GAB2 mRNA levels in 249 brains and found that decreased neurofibrillary tangle (r = -0.34, p = 0.0006) and senile plaque counts (r = -0.32, p = 0.001) were both good predictors of increased GAB2 mRNA levels albeit that sex (r = -0.28, p = 0.005) may have been a contributing factor. In summary, we hypothesise that GAB2 variants that are protective against LOAD in some populations may act functionally to increase GAB2 mRNA levels (in lymphoblastoid cells) and that increased GAB2 mRNA levels are associated with significantly decreased LOAD pathology. These findings support the hypothesis that Gab2 may protect neurons against LOAD but due to significant population heterogeneity, it is still unclear whether this protection is detectable at the genetic level.
    PLoS ONE 01/2013; · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Twenty years have passed since the foundational article of what is now known as evolutionary medicine (EM) was published. This young medical discipline examines, following Darwinian principles, susceptibility to certain diseases and how we react to them. In short, EM analyzes the final cause of the disease from a historical perspective.Over the years, EM has been introduced in various medical areas in very different ways. While it has found a role in some fields such as infectious diseases and oncology, its contribution in other areas has been quite limited. In endocrinology, EM has only gained prominence as a basis for the so-called “diseases of civilization”, including diabetes mellitus and obesity. However, many experts suggest that it may have a much higher potential. The aim of this paper is to provide a view about what evolutionary medicine is. Some examples of how EM may contribute to progress of our specialty are also given. There is no doubt that evolution enriches medicine, but medicine also offers knowledge to evolution.
    Endocrinología y Nutrición 01/2012;

Full-text (2 Sources)

Available from
Jun 2, 2014