论文     首页 > 科研成果 > 论文
Complement C7 is a Novel Risk Gene for Alzheimer's Disease in Han Chinese
论文题目: Complement C7 is a Novel Risk Gene for Alzheimer's Disease in Han Chinese
作者: Zhang DF, Fan Y, Xu M, Wang G, Wang D, Li J, Kong LL, Zhou H, Luo R, Bi R, Wu Y, Li GD; Alzheimer's Disease Neuroimaging Initiative (ADNI), Li M, Luo XJ, Jiang HY, Tan L, Zhong C, Fang Y, Zhang C, Sheng N, Jiang T, Yao YG
联系作者: yaoyg@mail.kiz.ac.cn
发表年度: 2019
DOI: doi: 10.1093/nsr/nwy127
摘要:

Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer'sdisease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10-6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10-7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and β-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese

刊物名称: National Science Review
论文出处: https://academic.oup.com/nsr/article/6/2/257/5161244#
影响因子: 9.408(2017年)
Copyright © 2018-2019 中国科学院昆明动物研究所 .All Rights Reserved
地址:云南省昆明市五华区教场东路32号  邮编:650223
电子邮件:zhanggq@mail.kiz.ac.cn  滇ICP备05000723号