Evidence map›Paper›PMID 30911067›Full record

ArticleScientific reports2019

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

Jose Pablo Miramontes-Gonzalez, C Makena Hightower, Kuixing Zhang, Hiroki Kurosaki, Andrew J Schork, Nilima Biswas, Sucheta Vaingankar, Manjula Mahata, Michael S Lipkowitz, Caroline M Nievergelt and 6 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Deriving psychiatric symptom-based biomarkers from multivariate relationships between psychophysiological and biochemical measures.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022
    Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 3 countries.

Jose Pablo Miramontes-GonzalezDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA. jpmiramontes@hotmail.com.
C Makena HightowerDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Kuixing ZhangDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Hiroki KurosakiDepartment of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Andrew J SchorkDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Nilima BiswasDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Sucheta VaingankarDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Manjula MahataDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Michael S LipkowitzGeorgetown University, Washington, DC, USA.
Caroline M NievergeltDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5766-8923
Dewleen G BakerDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Michael G ZieglerDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
David León-JiménezDepartment of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Rogelio González-SarmientoDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
Hiroshi IchinoseDepartment of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Daniel T O'ConnorDepartments of Medicine, Pharmacology, Psychiatry, and Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
University of California San Diego · USTokyo Institute of Technology · JPGeorgetown University · USVA San Diego Healthcare System · 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 O'CONNOR, DANIEL T · 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 CLINICAL AND TRANSLATIONAL RESEARCH INSTITUTEUL1RR031980 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2010 to 2011
$14.0M
San Diego EXPORT Comprehensive NCMHD Research CenterP60MD000220 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VILLARREAL, FRANCISCO · 2002 to 2011
$11.0M
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 TR000100NCRR NIH HHS UL1 RR031980NHLBI NIH HHS P01 HL058120NIDDK NIH HHS P30 DK079337NIDDK NIH HHS R01 DK094894NIMHD NIH HHS P60 MD000220
6 · The paper itself

Abstract

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease.

Identifiers

PMID30911067
PMCPMC6433864
OpenAlexW2925097082

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.