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1篇 您的检索式:作者名="Hejiang Zhou"
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1Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese显示文摘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's disease,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,P_(combined)=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.Deng-Feng Zhang Yu Fan Min Xu Guihong Wang Dong Wang Jin Li Li-Li Kong Hejiang Zhou Rongcan Luo Rui Bi Yong Wu Guo-Dong Li Ming Li Xiong-Jian Luo Hong-Yan Jiang Liwen Tan Chunjiu Zhong Yiru Fang Chen Zhang Nengyin Sheng Tianzi Jiang Yong-Gang Yao 2019National Science Review2019,6,2:6
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