机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academyof Sciences, Kunming 650223, China[2]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China[3]Department ofBiochemistry and Molecular Biology and Key Laboratory of Molecular Biology, School of Basic Medicine and Life Sciences, Hainan Medical College, Haikou 571199, China[4]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China[5]Department of Psychiatry, the First Affiliated Hospital of KunmingMedical University, Kunming 650032, China内科科室精神科昆明医科大学附属第一医院[6]Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha 410011, China昆明医科大学附属第一医院[7]The Mental HealthCenter and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610064, China四川大学华西医院[8]Division of Mood Disorders, Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China四川大学华西医院[9]Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences,Shanghai 200031, China四川大学华西医院[10]KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, Yunnan 650223, China
Alzheimer's disease (AD) is the most common cause of dementia. Mitochondrial dysfunction has been widely reported in AD due to its important role in cellular metabolism and energy production. Complex IV (cytochrome c oxidase, COX) of mitochondrial electron transport chain, is particularly vulnerable in AD. Defects of COX in AD have been well documented, but there is little evidence to support the genetic association of the COX-related genes with AD. In this study, we investigated the genetic association between 17 nuclear-encoded COX-related genes and AD in 1572 Han Chinese. The whole exons of these genes were also screened in 107 unrelated AD patients with a high probability of hereditarily transmitted AD. Variants in COX6B1, NDUFA4, SURF1, and COX10 were identified to be associated with AD. An integrative analysis with data of eQTL, expression and pathology revealed that most of the COX-related genes were significantly downregulated in AD patients and mouse models, and the AD-associated variants in COX6B1, SURF1, and COX10 were linked to altered mRNA levels in brain tissues. Furthermore, mRNA levels of Ndufa4, Cox5a, Cox10, Cox6b2, Cox7a2, and Lrpprc were significantly correlated with A beta plaque burden in hippocampus of AD mice. Convergent functional genomics analysis revealed strong supportive evidence for the roles of COX6B1, COX10, NDUFA4, and SURF1 in AD. As the result of our comprehensive analysis of the COX-related genes at the genetic, expression, and pathology levels, we have been able to provide a systematic view for understanding the relationships of the COX-related genes in the pathology of AD.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31730037, 81601124, 81560230]; National Natural Science Foundation of Yunnan Province [2015FB180]; Key Research Program of Frontier Sciences, Chinese Academy of Sciences [QYZDJ-SSW-SMC005]; Project for International Collaboration of the Bureau of International Collaboration, CAS [GJHZ1846]
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academyof Sciences, Kunming 650223, China[2]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
通讯作者：
通讯机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academyof Sciences, Kunming 650223, China[2]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China[4]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China[9]Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences,Shanghai 200031, China[10]KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, Yunnan 650223, China
推荐引用方式(GB/T 7714)：
Bi Rui,Zhang Wen,Zhang Deng-Feng,et al.Genetic association of the cytochrome c oxidase-related genes with Alzheimer's disease in Han Chinese[J].NEUROPSYCHOPHARMACOLOGY.2018,43(11):2264-2276.doi:10.1038/s41386-018-0144-3.
APA：
Bi, Rui,Zhang, Wen,Zhang, Deng-Feng,Xu, Min,Fan, Yu...&Yao, Yong-Gang.(2018).Genetic association of the cytochrome c oxidase-related genes with Alzheimer's disease in Han Chinese.NEUROPSYCHOPHARMACOLOGY,43,(11)
MLA：
Bi, Rui,et al."Genetic association of the cytochrome c oxidase-related genes with Alzheimer's disease in Han Chinese".NEUROPSYCHOPHARMACOLOGY 43..11(2018):2264-2276
医学