Send to

Choose Destination
See comment in PubMed Commons below
Neurobiol Aging. 2012 Jan;33(1):203.e25-33. doi: 10.1016/j.neurobiolaging.2010.08.002. Epub 2010 Sep 23.

Association and heterogeneity at the GAPDH locus in Alzheimer's disease.

Author information

  • 1Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.


Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogs were implicated in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. We genotyped 3 previously reported single nucleotide polymorphisms (SNPs; rs3741916-GAPDH 5' UTR, rs2029721-pGAPD, and rs4806173-GAPDHS) in 3 case-control series (2112 cases and 3808 controls). Rs3741916 showed the strongest LOAD association (p = 0.003). The minor allele of rs3741916 showed a protective effect in our combined series (odds ratio [OR] = 0.87%, 95% confidence interval [CI] = 0.79-0.96). This is consistent with results from the 2 published follow-up studies and in opposite direction of the original report. Meta-analysis of the published series with ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of only the follow-up series including ours revealed a significant protective effect for the minor allele of rs3741916 (OR = 0.85%, 95% CI = 0.76-0.96, p = 0.009). Our results support the presence of LOAD variants and heterogeneity at the GAPDH locus. The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center