ArticleAmerican journal of hypertension2011
Human dopamine β-hydroxylase promoter variant alters transcription in chromaffin cells, enzyme secretion, and blood pressure.
Article in American journal of hypertension, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter.Human molecular genetics · 2014Pooled it
- Heritable influence of DBH on adrenergic and renal function: twin and disease studies.PloS one · 2013Pooled it
- Multifactor Dimensionality Reduction Analysis to Evaluate the Association of Dopamine Beta-Hydroxylase (DΒH) Polymorphisms with Susceptibility to Dementia (SADEM Study).Molecular neurobiology · 2023Article
- Chiropractic care for hypertension: Review of the literature and study of biological and genetic bases.Acta bio-medica : Atenei Parmensis · 2020Review
- Association of regulatory variants of dopamine β-hydroxylase with cognition and tardive dyskinesia in schizophrenia subjects.Journal of psychopharmacology (Oxford, England) · 2020Article
- A High-Affinity Fluorescent Sensor for Catecholamine: Application to Monitoring Norepinephrine Exocytosis.Angewandte Chemie (International ed. in English) · 2019Article
- Effects of transgenic expression of dopamine beta hydroxylase (Dbh) gene on blood pressure in spontaneously hypertensive rats.Physiological research · 2016Article
- Human Bacterial Artificial Chromosome (BAC) Transgenesis Fully Rescues Noradrenergic Function in Dopamine β-Hydroxylase Knockout Mice.PloS one · 2016Article
- Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity.Circulation research · 2014Article
- Imputing observed blood pressure for antihypertensive treatment: impact on population and genetic analyses.American journal of hypertension · 2014Article
- Selective catecholamine recognition with NeuroSensor 521: a fluorescent sensor for the visualization of norepinephrine in fixed and live cells.ACS chemical neuroscience · 2013Article
- Disorders of blood pressure regulation-role of catecholamine biosynthesis, release, and metabolism.Current hypertension reports · 2012Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDopamine β-hydroxylase (DBH) plays an indispensable role in catecholamine synthesis by converting dopamine into norepinephrine. Here, we characterized a DBH promoter polymorphism (C-2073T; rs1989787; minor allele frequency ~16%) that influences not only gene transcription but also enzyme secretion and blood pressure (BP) in vivo.
methodsPlasma DBH activity was measured spectrophotometrically. DBH genetic effects on BP were tested in subjects with the most extreme BP values in a large primary care population. Functional effects of promoter variants were studied by site-directed mutagenesis in DBH promoter haplotype/luciferase reporter plasmids transfected into chromaffin cells. Sequence motifs were predicted from position weight matrices, and endogenous transcription factor binding was probed by Chromatin ImmunoPrecipitation (ChIP).
resultsThe T-allele of common promoter variant C-2073T was contained in a promoter haplotype that associated with plasma DBH activity, a trait also predicted by that variant itself. Promoter haplotypes including C-2073T predicted BP in the population, and the effect was also referable to C-2073T itself. Computationally, C-2073 disrupted a predicted match for transcription factor c-FOS. Site-directed mutagenesis at C-2073T altered not only basal promoter activity, but also transactivation by c-FOS, as well as the chromaffin cell secretory stimuli nicotine or pituitary adenylate cyclase-activating polypeptide (PACAP). Endogenous c-FOS bound to the motif in chromatin.
conclusionsThese results suggest that DBH promoter variant C-2073T is functional in vivo: this promoter variant seems to initiate a cascade of transcriptional and biochemical changes including augmented DBH secretion, eventuating in elevation of basal BP, and hence cardiovascular risk. The observations suggest new strategies for probing the pathophysiology, risk, and treatment of hypertension.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.