Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer's disease in Han Chinese

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 重大疾病机理的遗传学

	Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer's disease in Han Chinese
	Bi R 1,2; Zhang W 1; Yu DD 1; Li X 1,2; Wang HZ 1,3; Hu QX 1,2; Zhang C 4; Lu WH 4; Ni JL 5; Fang YR 4
刊名	NEUROBIOLOGY OF AGING
	2015
卷号	36 期号:3 页码:1604(e7-e16)
关键词	Alzheimer's disease mtDNA haplogroup Chinese Genetic susceptibility
通讯作者	ygyaozh@gmail.com
英文摘要	Mitochondrial dysfunction has been widely reported in psychiatric and neurodegenerative diseases. We aimed to investigate the association between matrilineal structures of Han Chinese populations and Alzheimer's disease (AD) by a 2-stage case-control study: A total of 341 AD patients and 435 normal individuals from Southwest China were analyzed for mitochondrial DNA sequence variations and were classified into respective haplogroups. A total of 371 AD patients and 470 normal individuals from East China, as validation samples, were genotyped for the variants defining the risk haplogroup. Haplogroup B5 had a significantly higher frequency in AD patients (7.33%) than in control subjects (3.68%) from Southwest China, and we found a similar pattern of higher frequency of B5 in patients in the case-control sample from East China. In the combined population, association of haplogroup B5 with AD risk was strengthened (p = 0.02; odds ratio = 1.74; 95% confidence interval = 1.10-2.76). In lymphoblastoid cell lines belonging to haplogroup B5a, we observed significantly increased reactive oxygen species and decreased mitochondrial mass. Hela cells with stable expression of the MT-ATP6 gene with B5-defining variant m.8584G>A also showed a significantly decreased mitochondrial function. Taken together, our results indicated that haplogroup B5 conferred genetic susceptibility to AD in Han Chinese, and this effect was most likely mediated by ancient variant m.8584G>A. The predisposing effect of B5 to AD is consistent with the ancestral-susceptibility model of complex diseases.
收录类别	SCI
资助信息	This study was supported by the Strategic Priority Research Program of Chinese Academy of Sciences (XDB02020000), the MOST of China (2011CB910902), and the National Natural Science Foundation of China (31171225 and 30925021).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9193]
专题	昆明动物研究所_重大疾病机理的遗传学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China 3.School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China 4.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong, University School of Medicine, Shanghai, China 5.First Geriatric Department, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China 6.The Mental Health Center & Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China
推荐引用方式 GB/T 7714	Bi R,Zhang W,Yu DD,et al. Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer's disease in Han Chinese[J]. NEUROBIOLOGY OF AGING,2015,36(3):1604(e7-e16).
APA	Bi R.,Zhang W.,Yu DD.,Li X.,Wang HZ.,...&Yao YG[*].(2015).Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer's disease in Han Chinese.NEUROBIOLOGY OF AGING,36(3),1604(e7-e16).
MLA	Bi R,et al."Mitochondrial DNA haplogroup B5 confers genetic susceptibility to Alzheimer's disease in Han Chinese".NEUROBIOLOGY OF AGING 36.3(2015):1604(e7-e16).