P1‐058: Association of glyceraldehyde‐3‐phosphate dehydrogenase locus variant with late‐onset Alzheimer's disease
Year: 2010
Type: article
Study design: Observational Study
Abstract: Previous studies have implicated variants in glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogues in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. Our objective is to explore the associations between GAPDH, its paralogues and LOAD. We genotyped three previously reported SNPs (rs3741916 in GAPDH, rs2029721 in pGAPD and rs4806173 in GAPDHS) and 22 additional SNPs, at the GAPDH and GAPDHS loci, in three case-control series collectively composed of 2112 cases and 3808 controls. We tested these SNPs for association with LOAD using multivariable logistic regression analysis adjusting for age, gender and ApoE. We performed meta-analysis of the most significant rs3741916 SNP using previously published series and ours. GAPDH variant rs3741916, which resides in the 5'UTR of this gene, showed the strongest evidence of association with LOAD (p value = 0.003). None of the other SNPs were as significant. The minor G allele showed a protective effect in our combined series (OR = 0.87, 95% confidence interval (CI) = 0.79-0.96). This result is consistent with all of the published follow-up series but is in the opposite direction to three of the four series from the original report. Combined meta-analysis of all published series with available data and ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of the 4 follow-up series with available data, including ours, revealed a significant protective effect for the minor G allele of rs3741916 (OR = 0.85, 95% CI = 0.76-0.96, p value = 0.0094). Our results provide supportive evidence for the presence of LOAD risk variants in the vicinity of GAPDH. The most promising variant (rs3741916) is unlikely to be the functional variant given opposing effects in different series. To provide greater understanding of the AD association at this heterogeneous locus, we intend to genotype this SNP in additional case-control series to further increase our sample size. Identification of the functional variant(s) in this region likely awaits deep variant discovery efforts.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1997855038