ArticleCirculation research2014
Regulatory polymorphisms in human DBH affect peripheral gene expression and sympathetic activity.
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In one paragraph
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 22% of its field
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.Molecular psychiatry · 2018Pooled it
- Pharmacogenetics of Dopamine β-Hydroxylase in cocaine dependence therapy with doxazosin.Addiction biology · 2019Trial
- C2CD5 in noradrenergic neurons regulates thermogenesis and lipid homeostasis via norepinephrine secretion.iScience · 2026Article
- Decellularization of various tissues and organs through chemical methods.Tissue & cell · 2024Review
- Effect of rs1108580 of DBH and rs1006737 of CACNA1C on Cognition and Tardive Dyskinesia in a North Indian Schizophrenia Cohort.Molecular neurobiology · 2023Article
- Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease.Frontiers in genetics · 2023Article
- The Presynaptic Regulation of Dopamine and Norepinephrine Synthesis Has Dissociable Effects on Different Kinds of Cognitive Conflicts.Molecular neurobiology · 2019Article
- Quantification of allelic differential expression using a simple Fluorescence primer PCR-RFLP-based method.Scientific reports · 2019Article
- Testing genetic modifiers of behavior and response to atomoxetine in autism spectrum disorder with ADHD.Journal of developmental and physical disabilities · 2018Article
- Regulatory Variants Modulate Protein Kinase C α (PRKCA) Gene Expression in Human Heart.Pharmaceutical research · 2017Article
- Methylation polymorphism influences practice effects in children during attention tasks.Cognitive neuroscience · 2017Article
- The influence of dopamine-beta-hydroxylase and catecholDiabetology & metabolic syndrome · 2017Article
- The dopamine β-hydroxylase gene in Chinese goose (Anas cygnoides): cloning, characterization, and expression during the reproductive cycle.BMC genetics · 2016Article
- Human Bacterial Artificial Chromosome (BAC) Transgenesis Fully Rescues Noradrenergic Function in Dopamine β-Hydroxylase Knockout Mice.PloS one · 2016Article
- Analyzing allele specific RNA expression using mixture models.BMC genomics · 2015Article
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Authors and funding
17 authors at 8 institutions in 1 country.
Elizabeth S BarrieFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
David WeinshenkerFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Anurag VermaFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Sarah A PendergrassFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Leslie A LangeFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Marylyn D RitchieFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
James G WilsonFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Helena KuivaniemiFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Gerard TrompFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
David J CareyFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Glenn S GerhardFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Murray H BrilliantFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Scott J HebbringFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Joseph F CubellsFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Julia K PinsonneaultFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Greg J NormanFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.).
Wolfgang SadeeFrom the Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus (E.S.B., J.K.P., W.S.); Department of Human Genetics, Emory University School of Medicine, Atlanta, GA (D.W., J.F.C.); Center for Systems Genomics, Pennsylvania State University, University Park (A.V., S.A.P., M.D.R.); Department of Genetics, University of North Carolina School of Medicine, Chapel Hill (L.A.L.); Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.); The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA (H.K., G.T., D.J.C.); Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey (G.S.G.); Center for Human Genetics, Marshfield Clinic Research Foundation, WI (M.H.B., S.J.H.); and Department of Psychology, The University of Chicago, IL (G.J.N.). wolfgang.sadee@osumc.edu.
Pennsylvania State University · USMarshfield Clinic · USUniversity of Mississippi Medical Center · USUniversity of North Carolina at Chapel Hill · USCenter for Human Genetics · USEmory University · USGeisinger Health System · USPenn State Milton S. Hershey Medical Center · US
Funding
Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2MUniversity of Iowa Clinical and Translational Science Program (TL1)UL1RR025755 · NCRR · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2008 to 2011
$26.3MPHARMACOGENOMICS OF ARRHYTHMIA THERAPYU01HL065962 · NHLBI · VANDERBILT UNIVERSITY · PI RODEN, DAN M · 2001 to 2009
$24.8MThe Ohio State University Center for clinical and Translational ScienceUL1TR001070 · NCATS · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2013 to 2017
$22.6MPharmacogenomic Evaluation of Antihypertensive ResponsesU01GM074492 · NIGMS · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2005 to 2014
$20.7MPharmacogenomics of Arrhythmia TherapyU19HL065962 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RODEN, DAN M · 2010 to 2014
$17.4MTISSUE DISTRIBUTION FOR RARE DISEASE RESEARCHU42RR006042 · NCRR · NATIONAL DISEASE RESEARCH INTERCHANGE · PI LONSDALE, JOHN T · 1991 to 2011
$16.5MExpression Genetics in Drug TherapyU01GM092655 · NIGMS · OHIO STATE UNIVERSITY · PI SADEE, WOLFGANG · 2010 to 2014
$8.6MENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8MIRIS: Incorporating Research Into SightU01HG006389 · NHGRI · ESSENTIA INSTITUTE OF RURAL HEALTH · PI MCCARTY, CATHERINE ANNE · 2011 to 2014
$4.1MNCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1TR000427NCATS NIH HHS UL1 TR001070NCRR NIH HHS 5 U42 RR006042-20NCRR NIH HHS U42 RR006042NCRR NIH HHS UL1 RR025755NCRR NIH HHS UL1RR025755NHGRI NIH HHS 1U01HG006389-01NHGRI NIH HHS U01 HG006389NHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS U01 HL065962NHLBI NIH HHS U01HL065962NHLBI NIH HHS U19 HL065962NIGMS NIH HHS U01 GM074492NIGMS NIH HHS U01 GM092655NINDS NIH HHS P30 NS055077NINDS NIH HHS P30NS055077
Abstract
rationaleDopamine β-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine in the central nervous system and peripherally. DBH variants are associated with large changes in circulating DBH and implicated in multiple disorders; yet causal relationships and tissue-specific effects remain unresolved.
objectiveTo characterize regulatory variants in DBH, effect on mRNA expression, and role in modulating sympathetic tone and disease risk. METHODS AND
resultsAnalysis of DBH mRNA in human tissues confirmed high expression in the locus coeruleus and adrenal gland, but also in sympathetically innervated organs (liver>lung>heart). Allele-specific mRNA assays revealed pronounced allelic expression differences in the liver (2- to 11-fold) attributable to promoter rs1611115 and exon 2 rs1108580, but only small differences in locus coeruleus and adrenals. These alleles were also associated with significantly reduced mRNA expression in liver and lung. Although DBH protein is expressed in other sympathetically innervated organs, mRNA levels were too low for analysis. In mice, hepatic Dbh mRNA levels correlated with cardiovascular risk phenotypes. The minor alleles of rs1611115 and rs1108580 were associated with sympathetic phenotypes, including angina pectoris. Testing combined effects of these variants suggested protection against myocardial infarction in 3 separate clinical cohorts.
conclusionsWe demonstrate profound effects of DBH variants on expression in 2 sympathetically innervated organs, liver and lung, but not in adrenals and brain. Preliminary results demonstrate an association of these variants with clinical phenotypes responsive to peripheral sympathetic tone. We hypothesize that in addition to endocrine effects via circulating DBH and norepinephrine, the variants act in sympathetically innervated target organs.
Indexed as
Polymorphism, Single NucleotideAllelic ImbalanceAnimalsCardiovascular DiseasesDopamine beta-HydroxylaseExonsFemaleGene Expression Regulation, EnzymologicGenetic Predisposition to DiseaseHeartHumansLiverLungMaleMicePhenotypeDopamine beta-HydroxylaseRNA, Messengerdopamine β-hydroxylasegene expression/regulationgenetic associationgenetic polymorphismhumanmyocardial infarction
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