Presence of mutation m.14484T > C in a Chinese family with maternally inherited essential hypertension but no expression of LHON

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

	Presence of mutation m.14484T > C in a Chinese family with maternally inherited essential hypertension but no expression of LHON
	Guo H 1,2; Zhuang XY 1; Guo L 4; Yu DD 1; Liu J 4; Yang DK 4; Yao YG[*]1; Zhang AM 1; Zhang W 1,3; Yuan Y 4
刊名	BIOCHIMICA ET BIOPHYSICA ACTA
	2012
卷号	1822 期号:10 页码:1535-1543
关键词	Essential hypertension mtDNA m.14484T > C Chinese Arterial stiffness LHON
通讯作者	ygyaozh@gmail.com
合作状况	其它
英文摘要	Essential hypertension (EH. MIM 145500) is the most common cardiovascular disease and affects one-quarter of the world's adult population. Families with EH in a mode of maternal transmission have been occasionally observed in clinical settings and suggested an involvement of mitochondrial DNA (mtDNA) mutation. We aimed to characterize the role of mtDNA mutation in EH. We reported a large Han Chinese family with a maternally inherited EH and an extraordinarily high percentage of sudden death mainly in affected females. Analysis of the entire mtDNA genome of the proband identified a homoplasmic primary mutation m.14484T>C for Leber's hereditary optic neuropathy (WON), along with several variants indicating haplogroup F1 status. Intriguingly, no maternal member in this family had WON though they all harbored m.14484T>C The arterial stiffness of the members carrying mutation m.14484T>C was significantly increased than that of non-maternal members without this mutation. No environmental factor (including age, sex, smoking, diabetes, hyperlipidemia) was correlated with the decreased aortic elastic properties observed in affected members. Mitochondrial respiration rate and membrane potential (Delta Psi(m)) were significantly reduced in lymphoblastoid cell lines established from affected members carrying m.14484T>C when compared to control cell lines (P<0.05). There was an elevation of reactive oxygen species and a compensatory increase of mitochondrial mass in mutant cell lines. Our results suggest that m.14484T>C causes EH under certain circumstance. This study provides a paradigm for diverse phenotypes of the primary WON mutation and suggests for the necessity of routine cardiac evaluation in patients with the primary WON mutation.
收录类别	SCI
资助信息	This work wassupported by the Ministry of Science and Technology of China (2011CB910900), the National Natural Science Foundation of China (30925021), Yunnan Province (2009CI119 and 2011Z044), and the Chinese Academy of Sciences.
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9577]
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 Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, China 2.Department of Cardiology, Calmette Hospital, Kunming Medical University, Kunming, China 3.Graduate School of the Chinese Academy of Sciences, Beijing, China 4.The Second Affiliated Hospital of Kunming Medical University
推荐引用方式 GB/T 7714	Guo H,Zhuang XY,Guo L,et al. Presence of mutation m.14484T > C in a Chinese family with maternally inherited essential hypertension but no expression of LHON[J]. BIOCHIMICA ET BIOPHYSICA ACTA,2012,1822(10):1535-1543.
APA	Guo H.,Zhuang XY.,Guo L.,Yu DD.,Liu J.,...&Yuan Y.(2012).Presence of mutation m.14484T > C in a Chinese family with maternally inherited essential hypertension but no expression of LHON.BIOCHIMICA ET BIOPHYSICA ACTA,1822(10),1535-1543.
MLA	Guo H,et al."Presence of mutation m.14484T > C in a Chinese family with maternally inherited essential hypertension but no expression of LHON".BIOCHIMICA ET BIOPHYSICA ACTA 1822.10(2012):1535-1543.