Abstract
Microtubule-associated protein tau (MAPT) gene is compelling among the susceptibility genes of neurodegenerative diseases which include Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Our meta-analysis aimed to find the association between MAPT and the risk of these diseases. Published literatures were retrieved from MEDLINE and other databases, and 82 case-control studies were recruited. Six haplotype tagging single-nucleotide polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9 and rs7521) and haplotypes (H2 and H1c) were significantly associated with the above diseases. The odds ratios (ORs) and 95 % confidence intervals (CIs) were evaluated by comparison in minor and major allele frequency using the R software. This study demonstrated that different variants in MAPT were associated with AD (rs2471738: OR= 1.04, 95%CI = 1.00 - 1.09; H2: OR = 0.94, 95% CI = 0.91 - 0.97), PD (H2: OR = 0.76, 95% CI = 0.74 - 0.79), PSP (rs242557: OR = 1. 96, 95% CI = 1. 71 - 2.25; rs2471738: OR = 1. 85, 95% CI = 1. 48 - 2.31; H2: OR = 0.20, 95% CI = 0.18 - 0.23), CBD (rs242557: OR = 2.51, 95%CI = 1. 66 -3.78; rs2471738: OR = 2.07, 95%CI = 1. 32 -3.23; H2: OR = OR = 0.30, 95% CI = 0.23 - 0.41) and ALS (H2: OR = 0.92, 95% CI = 0.86 - 0.98) instead of FTD (H2: OR = 1.02, 95% CI = 0.78 - 1.32). In conclusion, MAPT is associated with risk of neurodegenerative diseases, suggesting crucial roles of tau in neurodegenerative processes.
Highlights
Neurodegenerative diseases are a group of disorders with progressive neuronal loss in particular regions of brain, including Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and many others
Two studies did not state the diagnostic criteria of AD, and 15 studies did not state whether the polymorphisms were in Hardy-Weinberg equilibrium (HWE)
Our meta-analysis showed that the minor allele (T allele) within rs2471738 was mildly associated with an increased risk of AD (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.00 - 1.09) and H2 haplotype might be a protective factor for AD (OR = 0.94, 95% confidence intervals (CIs) = 0.91 0.97) (Figure 2; Supplementary Table 8)
Summary
Neurodegenerative diseases are a group of disorders with progressive neuronal loss in particular regions of brain, including Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and many others. The etiology of neurodegenerative diseases is complicated and multifactorial, mainly including genetic variants and environmental exposure. Epidemiologic evidence for the association between the environmental exposure and neurodegenerative diseases is not conclusive [1]. Genetic variant is a crucial factor in etiology and pathogenic mechanisms of neurodegenerative diseases [2]. Hundreds of genetic variants have been confirmed significantly associated with neurodegenerative diseases, but the majority of these genes do not overlap across diseases [2]. Mutations in MAPT have been reported to participate in AD [4,5,6], PD [7,8,9], PSP [10, 11], CBD [12, 13], FTD [14, 15] and ALS [16, 17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
