Abstract
Published studies revealed that the microtubule-associated protein tau (MAPT) gene polymorphisms increased Alzheimer’s disease (AD) risk; the associations of 4 single nucleotide polymorphisms (SNPs, rs242557G/A, rs2471738C/T, rs3785883G/A and rs1467967A/G) of the MAPT gene with AD risk, however, remain inconclusive. Here, we conducted a meta-analysis to investigate the relationship between the MAPT SNPs and AD risk. A significant association of SNP rs242557 with AD risk was found in a dominant [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.01, 1.10, P = 0.025] genetic model, and a suggestive association in an allelic (OR = 1.03, 95% CI = 1.00, 1.06, P = 0.078). When APOE epsilon 4 carrier status was included in stratified analysis, this association was even stronger (allelic model for the APOE epsilon 4 positive individuals: OR = 1.24, 95% CI = 1.08, 1.43, P = 0.003). Furthermore, a significant association of SNP rs2471738 with AD risk was found under all the four models (allelic: OR = 1.11, 95% CI = 1.01, 1.20, P = 0.021; dominant: OR = 1.10, 95% CI = 1.00, 1.21, P = 0.046; recessive: OR = 1.18, 95% CI = 1.05, 1.32, P = 0.004; additive: OR = 1.20, 95% CI = 1.07, 1.34, P = 0.002) models. However, pooled results suggest that the neither rs3785883 nor rs1467967 is associated with AD risk under all the four genetic models. In summary, our study provides further evidence of the associations of the MAPT SNPs with AD risk.
Highlights
One of the neuropathological hallmarks of Alzheimer’s Disease (AD) is the neurofibrillary tangle, which contains paired helical filaments (PHFs) composed of hyperphosphorylated forms of the microtubuleassociated protein tau (MAPT) by mechanism which is not illustrated [1]
Some studies were showed that SNPs rs242557 [4, 5], rs3785883 [6] in US series, rs2471738 [6, 7] and rs1467967 [8] of the MAPT gene might been associated with increased AD risk
We evaluated the genetic heterogeneity of the studies included and carried out www.impactjournals.com/oncotarget a meta-analysis on the association between the MAPT SNPs with AD risk to make a more accurate assessment of the relationship for greater power in detecting the disease associations
Summary
One of the neuropathological hallmarks of Alzheimer’s Disease (AD) is the neurofibrillary tangle, which contains paired helical filaments (PHFs) composed of hyperphosphorylated forms of the microtubuleassociated protein tau (MAPT) by mechanism which is not illustrated [1]. Increasing attention has been paid to endogenous and exogenous factors, as well as genetic risk factors contributing to the incidence of AD [2], stimulating the disease progression of AD [3]. There have been conflicting results showing positive or negative findings on the association between the MAPT SNPs and AD risk. Some studies were showed that SNPs rs242557 [4, 5], rs3785883 [6] in US series, rs2471738 [6, 7] and rs1467967 [8] of the MAPT gene might been associated with increased AD risk. Some studies were reported that rs242557 [8,9,10], rs3785883 [11,12,13,14], rs2471738 [11, 14, 15] and rs1467967 [7, 16] might not be associated with AD risk [10, 11, 13, 16, 17]
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