Evidence map›Paper›PMID 24391727›Full record

SynthesisPloS one2013

Heritable influence of DBH on adrenergic and renal function: twin and disease studies.

Dalal N Pasha, Jason T Davis, Fangwen Rao, Yuqing Chen, Gen Wen, Maple M Fung, Manjula Mahata, Kuixing Zhang, Danuta Trzebinska, Maja Mustapic and 6 more

Erratum issuedOpen access · goldAbstract readMeta-AnalysisObservational StudyTwin Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Dalal N PashaDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Jason T DavisDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Fangwen RaoDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Yuqing ChenDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Gen WenDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Maple M FungDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Manjula MahataDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Kuixing ZhangDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Danuta TrzebinskaDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Maja MustapicDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
C Makena HightowerDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Michael S LipkowitzDepartment of Medicine, Georgetown University, Washington, District of Columbia, United States of America.
Ming JiGraduate School of Public Health, Division of Epidemiology and Biostatistics, San Diego State University, San Diego, California, United States of America.
Michael G ZieglerDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America.
Caroline M NievergeltDepartment of Psychiatry, University of California at San Diego, La Jolla, California, United States of America.
Daniel T O'ConnorDepartment of Medicine, University of California at San Diego, La Jolla, California, United States of America ; Department of Pharmacology, University of California at San Diego, La Jolla, California, United States of America ; Veterans Affairs San Diego Healthcare System, La Jolla, California, United States of America.
University of California, San Diego · USGeorgetown University · USSan Diego State University · US

Funding

San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
Trafficking of catecholamine storage vesicle proteinsP01HL058120 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZIEGLER, MICHAEL G. · 1999 to 2009
$18.5M
UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AGARWAL, ANUPAM · 2008 to 2022
$18.3M
San Diego EXPORT Comprehensive NCMHD Research CenterP60MD000220 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALEY, SANDRA P · 2002 to 2011
$11.0M
Genomic Predictors of Combat Stress Vulnerability and ResilienceR01MH093500 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIEVERGELT, CAROLINE M · 2011 to 2013
$2.7M
Hypertensive kidney disease: Novel pathogenic and therapeutic pathwayR01DK094894 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VAINGANKAR, SUCHETA M · 2012 to 2015
$1.4M
NCATS NIH HHS UL1 TR000100NHLBI NIH HHS HL58120NHLBI NIH HHS P01 HL058120NIDDK NIH HHS DK079337NIDDK NIH HHS P30 DK079337NIDDK NIH HHS R01 DK094894NIMHD NIH HHS MD000220NIMHD NIH HHS P60 MD000220NIMH NIH HHS R01 MH093500PHS HHS K094894
6 · The paper itself

Abstract

backgroundElevated sympathetic activity is associated with kidney dysfunction. Here we used twin pairs to probe heritability of GFR and its genetic covariance with other traits.

methodsWe evaluated renal and adrenergic phenotypes in twins. GFR was estimated by CKD-EPI algorithm. Heritability and genetic covariance of eGFR and associated risk traits were estimated by variance-components. Meta-analysis probed reproducibility of DBH genetic effects. Effect of DBH genetic variation on renal disease was tested in the NIDDK-AASK cohort.

resultsNorepinephrine secretion rose across eGFR tertiles while eGFR fell (p<0.0001). eGFR was heritable, at h(2) = 67.3±4.7% (p = 3.0E-18), as were secretion of norepinephrine (h(2) = 66.5±5.0%, p = 3.2E-16) and dopamine (h(2) = 56.5±5.6%, p = 1.8E-13), and eGFR displayed genetic co-determination (covariance) with norepinephrine (ρG = -0.557±0.088, p = 1.11E-08) as well as dopamine (ρG = -0.223±0.101, p = 2.3E-02). Since dopamine β-hydroxylase (DBH) catalyzes conversion of dopamine to norepinephrine, we studied functional variation at DBH; DBH promoter haplotypes predicted transcriptional activity (p<0.001), plasma DBH (p<0.0001) and norepinephrine (p = 0.0297) secretion; transcriptional activity was inversely (p<0.0001) associated with basal eGFR. Meta-analysis validated DBH haplotype effects on eGFR across 3 samples. In NIDDK-AASK, we established a role for DBH promoter variation in long-term renal decline rate (GFR slope, p = 0.003).

conclusionsThe heritable GFR trait shares genetic determination with catecholamines, suggesting new pathophysiologic, diagnostic and therapeutic approaches towards disorders of GFR as well as CKD. Adrenergic activity may play a role in progressive renal decline, and genetic variation at DBH may assist in profiling subjects for rational preventive treatment.

Indexed as

AdultBlack or African AmericanCohort StudiesDopamineDopamine beta-HydroxylaseFemaleGenetic VariationGlomerular Filtration RateHaplotypesHumansMaleMiddle AgedNorepinephrinePromoter Regions, GeneticRenal Insufficiency, ChronicDopamineDopamine beta-HydroxylaseNorepinephrine

Identifiers

PMID24391727
PMCPMC3876991
OpenAlexW2089119696

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.