Meta-analysis of the association between variants in MAPT and neurodegenerative diseases

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 singlenucleotide 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.