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学科主题临床医学
Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure
Chen, Yuqing7,8; Wen, Gen8; Rao, Fangwen8; Zhang, Kuixing8; Wang, Lei8; Rodriguez-Flores, Juan L.8; Sanchez, Amber P.8; Mahata, Manjula8; Taupenot, Laurent8; Sun, Ping8; Mahata, Sushil K.2,8; Tayo, Bamidele6; Schork, Nicholas J.4; Ziegler, Michael G.8; Hamilton, Bruce A.8; O′ Connor, Daniel T.1,2,3,5,8
关键词dopamine beta-hydroxylase hypertension polymorphism
刊名JOURNAL OF HYPERTENSION
2010
DOI10.1097/HJH.0b013e328332bc87
28期:1页:76-U26
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Peripheral Vascular Disease
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]INHIBITORY PEPTIDE CATESTATIN ; LINKAGE DISEQUILIBRIUM ; CARDIOVASCULAR REACTIVITY ; TRANSCRIPTION FACTORS ; CEREBROSPINAL-FLUID ; NERVOUS-SYSTEM ; GENETIC RISK ; HYPERTENSION ; ASSOCIATION ; DISEASE
英文摘要

Rationale Dopamine beta-hydroxylase (DBH) plays an essential role in catecholamine synthesis by converting dopamine into norepinephrine. Here we systematically investigated DBH polymorphisms associated with enzymatic activity as well as autonomic and blood pressure (BP)/disease phenotypes in vivo.

Methods and results Seventy genetic variants were discovered at the locus; across ethnicities, much of the promoter was spanned by a 5′ haplotype block, with a larger block spanning the promoter in whites than blacks. DBH secretion was predicted by genetic variants in the DBH promoter, rather than the amino acid coding region. The C allele of common promoter variant C-970T increased plasma DBH activity, epinephrine excretion, the heritable change in BP during environmental stress in twin pairs, and also predicted higher basal BP in three independent populations. Mutagenesis and expression studies with isolated/transfected DBH promoter/luciferase reporters in chromaffin cells indicated that variant C-970T was functional. C-970T partially disrupted consensus transcriptional motifs for n-MYC and MEF-2, and this variant affected not only basal expression, but also the response to exogenous/co-transfected n-MYC or MEF-2; during chromatin immunoprecipitation, these two endogenous factors interacted with the motif.

Conclusions These results suggest that common DBH promoter variant C-970T plays a role in the pathogenesis of human essential hypertension: common genetic variation in the DBH promoter region seems to initiate a cascade of biochemical and physiological changes eventuating in alterations of basal BP. These observations suggest new molecular strategies for probing the pathophysiology, risk, and rational treatment of systemic hypertension. J Hypertens 28: 76-86 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

语种英语
WOS记录号WOS:000273405900011
项目编号RR00827 ; MD000220
资助机构NIH/NCRR-supported General Clinical Research Center at UCSD ; NIH/NCMHD EXPORT minority health center
引用统计
被引频次:32[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63622
专题北京大学第一临床医学院_肾脏内科
作者单位1.VASDHS, La Jolla, CA 92093 USA
2.Peking Univ, Hosp 1, Div Renal, Beijing 100034, Peoples R China
3.Univ Calif San Diego, Sch Med, Dept Med 0838, La Jolla, CA 92093 USA
4.Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
5.Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
6.Univ Calif San Diego, Ctr Human Genet & Genom, La Jolla, CA 92093 USA
7.Loyola Univ, Chicago Med Ctr, Dept Epidemiol & Prevent Med, Maywood, IL USA
8.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
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GB/T 7714
Chen, Yuqing,Wen, Gen,Rao, Fangwen,et al. Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure[J]. JOURNAL OF HYPERTENSION,2010,28(1):76-U26.
APA Chen, Yuqing.,Wen, Gen.,Rao, Fangwen.,Zhang, Kuixing.,Wang, Lei.,...&Connor, Daniel T..(2010).Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure.JOURNAL OF HYPERTENSION,28(1),76-U26.
MLA Chen, Yuqing,et al."Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure".JOURNAL OF HYPERTENSION 28.1(2010):76-U26.
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