Rare Genetic Variants of the Transthyretin Gene Are Associated with 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

	Rare Genetic Variants of the Transthyretin Gene Are Associated with Alzheimer’s Disease in Han Chinese
	Xiang Q 1,2; Bi R[]1; Zheng C 4; Fang YR 4; Yao GY[]1,2,3; Xu M 1,2; Zhang DF 1; Tan LW 3
刊名	Molecular Neurobiology
	2016
卷号	期号:页码:published online
关键词	Alzheimer’sdisease TTR Rarevariant Genetic association Aβ-bindingability
通讯作者	birui@mail.kiz.ac.cn
合作状况	其它
英文摘要	Alzheimer's disease (AD) is the most prevalent form of dementia in the world. The neuropathological characteristics of AD patients are the accumulation of extracellular plaques of β-amyloid (Aβ) and intracellular hyperphosphorylated tau protein. Transthyretin (TTR) may alleviate AD symptom by reducing Aβ concentration in the brain. There were reports for a decreased TTR level in both AD brain and blood. However, there is still no robust evidence to support the genetic association of the TTR gene with AD. In this study, we aimed to investigate the potential association of TTR variation with AD by directly sequencing the whole exons and the promoter region of the TTR gene in 529 AD patients and 334 healthy controls from Han Chinese population. We found no association between TTR common variants and AD but observed an enrichment of TTR rarevariants in AD patients relative to controls. Further in silico prediction analysis and functional assessment at the cellular level identified four potentially pathogenic rare variants in AD patients. In particular, variant c.-239C>A could potentially downregulate the TTR promoter activity; c.200+4A>G might influence the constitutive splicing of TTR mRNA; c.148G>A (p.V50M) and c.332C>T (p.A111V) would change the structure of TTR and decrease its Aβ-binding ability. Our results provided direct genetic evidence to support the active involvement of TTR in AD.
收录类别	SCI
资助信息	Thisstudywas supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/10544]
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 ofAnimal Models and Human Disease Mechanisms oftheChineseAcademyofSciencesandYunnanProvince,Kunming Institute of Zoology, Kunming, Yunnan 650223, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China 3.TheInstituteof MentalHealth,theSecondXiangyaHospital,Central South University, Changsha, Hunan 410011, China 4.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China 5.CAS Center for Excellence in Brain Science and Intelligence Technology,ChineseAcademyofSciences,Shanghai200031,Chi
推荐引用方式 GB/T 7714	Xiang Q,Bi R[],Zheng C,et al. Rare Genetic Variants of the Transthyretin Gene Are Associated with Alzheimer’s Disease in Han Chinese[J]. Molecular Neurobiology,2016,(*):published online.
APA	Xiang Q.,Bi R[].,Zheng C.,Fang YR.,Yao GY[].,...&Tan LW.(2016).Rare Genetic Variants of the Transthyretin Gene Are Associated with Alzheimer’s Disease in Han Chinese.Molecular Neurobiology,(),published online.
MLA	Xiang Q,et al."Rare Genetic Variants of the Transthyretin Gene Are Associated with Alzheimer’s Disease in Han Chinese".Molecular Neurobiology .(2016):published online.