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微管相关蛋白tau(MAPT)基因变异与神经退行性疾病关联的荟萃分析。

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

作者信息

Zhang Cheng-Cheng, Zhu Jun-Xia, Wan Yu, Tan Lin, Wang Hui-Fu, Yu Jin-Tai, Tan Lan

机构信息

Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, PR China.

Clinical Skills Training Center, Qingdao Municipal Hospital, Qingdao University, PR China.

出版信息

Oncotarget. 2017 Jul 4;8(27):44994-45007. doi: 10.18632/oncotarget.16690.

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.

摘要

微管相关蛋白tau(MAPT)基因在神经退行性疾病的易感基因中备受关注,这些疾病包括阿尔茨海默病(AD)、帕金森病(PD)、进行性核上性麻痹(PSP)、皮质基底节变性(CBD)、额颞叶痴呆(FTD)和肌萎缩侧索硬化症(ALS)。我们的荟萃分析旨在寻找MAPT与这些疾病风险之间的关联。从MEDLINE和其他数据库中检索已发表的文献,并纳入了82项病例对照研究。六个单倍型标签单核苷酸多态性(rs1467967、rs242557、rs3785883、rs2471738、del-In9和rs7521)以及单倍型(H2和H1c)与上述疾病显著相关。使用R软件通过比较次要和主要等位基因频率来评估比值比(OR)和95%置信区间(CI)。本研究表明,MAPT中的不同变体与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 = 0.30,95%CI = 0.23 - 0.41)和ALS(H2:OR = 0.92,95%CI = 0.86 - 0.98)相关,而与FTD(H2:OR = 1.02,95%CI = 0.78 - 1.32)无关。总之,MAPT与神经退行性疾病风险相关,提示tau在神经退行性过程中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7474/5546535/7cb944df6703/oncotarget-08-44994-g001.jpg

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