Evidence map›Paper›PMID 25089948›Full record

Trial reportPharmacogenetics and genomics2014

Ancestry and other genetic associations with plasma PCSK9 response to simvastatin.

Elizabeth Theusch, Marisa W Medina, Jerome I Rotter, Ronald M Krauss

Open access · greenAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 3 pooled it
1.8field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 3 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Lipids, blood pressure and kidney update 2015.Lipids in health and disease · 2015
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 2 countries.

Elizabeth TheuschaChildren's Hospital Oakland Research Institute, Oakland bLos Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California, USA.
Marisa W Medina
Jerome I Rotter
Ronald M Krauss
PharmacoGenetics (China) · CN

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4M
UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Pharmacogenomics and Risk of Cardiovascular DiseaseU19HL069757 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI KRAUSS, RONALD M · 2010 to 2014
$12.8M
Alternative Splicing in Regulation of Cholesterol Synthesis and UptakeR01HL104133 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI MEDINA, MARISA WONG · 2010 to 2014
$2.0M
Genetic and Molecular Approaches To Cardiovascular DiseaseT32HL098057 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI KRAUSS, RONALD M · 2009 to 2013
$1.0M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NHLBI NIH HHS R01 HL104133NHLBI NIH HHS T32 HL098057NHLBI NIH HHS U19 HL069757NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

objectiveStatins stimulate transcription of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of the low-density lipoprotein receptor, thus blunting the cholesterol-lowering effects of statin treatment. Although there is interindividual variation in PCSK9 statin response, little is known about ancestral and other genetic factors that could contribute to this variation.

methodsWe measured plasma PCSK9 levels before and after 6 weeks of treatment with 40 mg/day simvastatin in 901 participants of the Cholesterol and Pharmacogenetics clinical trial and tested phenotypic and genetic factors for correlation with PCSK9 statin response.

resultsStatin-induced changes in plasma low-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B were all significantly correlated with statin-induced changes in PCSK9. A detailed examination of the associations of genetic ancestry with PCSK9 statin response revealed that Ashkenazi Jews had smaller statin-induced increases in PCSK9 levels than other self-reported Caucasians (P=0.016). Using genomewide association analysis, we found that the 'G' minor allele of rs13064411 in the WD repeat domain 52 (WDR52) gene was significantly associated with greater statin-induced increases in plasma PCSK9 in Caucasians (P=8.2 × 10(-8)) in the Cholesterol and Pharmacogenetics trial.

conclusionOverall, these results suggest that genetic ancestry and the rs13064411 genotype contribute to interindividual variation in PCSK9 statin response in Caucasians.

Indexed as

Polymorphism, Single NucleotideCytoskeletal ProteinsFemaleGenetic Association StudiesGenome-Wide Association StudyHumansJewsMaleNuclear ProteinsPeptide HydrolasesProprotein Convertase 9Proprotein ConvertasesRacial GroupsSelf ReportSerine EndopeptidasesSimvastatinCFAP44 protein, humanCytoskeletal ProteinsNuclear ProteinsPCSK9 protein, humanPeptide HydrolasesProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesSimvastatin

Identifiers

PMID25089948
PMCPMC4159722
OpenAlexW2327849580

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.