Evidence map›Paper›PMID 30325262›Full record

ArticlePharmacogenomics2018

RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms.

Paul J Isackson, Jianxin Wang, Mohammad Zia, Paul Spurgeon, Adrian Levesque, Jonathan Bard, Smitha James, Norma Nowak, Tae Keun Lee, Georgirene D Vladutiu

Abstract read
In one paragraph

Article in Pharmacogenomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Neurology · 2023
    Article
  8. Review
  9. Article
  10. Statins Neuromuscular Adverse Effects.International journal of molecular sciences · 2022
    Review
  11. Review
  12. Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy.International journal of molecular sciences · 2021
    Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. A Mechanism for Statin-Induced Susceptibility to Myopathy.JACC. Basic to translational science · 2019
    Article
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

10 authors.

Paul J IsacksonDepartment of Pediatrics, State University of New York at Buffalo, NY 14203, USA.
Jianxin WangCenter for Computational Research, State University of New York at Buffalo, NY 14203, USA.
Mohammad ZiaCenter for Computational Research, State University of New York at Buffalo, NY 14203, USA.
Paul SpurgeonCenter for Computational Research, State University of New York at Buffalo, NY 14203, USA.
Adrian LevesqueCenter for Computational Research, State University of New York at Buffalo, NY 14203, USA.
Jonathan BardCenter for Computational Research, State University of New York at Buffalo, NY 14203, USA.
Smitha JamesNew York State Center of Excellence in Bioinformatics & Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Norma NowakNew York State Center of Excellence in Bioinformatics & Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Tae Keun LeeDepartment of Pediatrics, State University of New York at Buffalo, NY 14203, USA.
Georgirene D VladutiuDepartment of Pediatrics, State University of New York at Buffalo, NY 14203, USA.

Funding

GENETIC SUSCEPTIBILITY TO LIPID-LOWERING DRUG-INDUCED MYOPATHIESR01HL085800 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI VLADUTIU, GEORGIRENE · 2008 to 2012
$2.0M
Role of Narexin in Neuromuscular DiseaseR21AR055704 · NIAMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI ISACKSON, PAUL J · 2008 to 2009
$384k
NHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS R01 HL085800NIAMS NIH HHS R21 AR055704
6 · The paper itself

Abstract

aimTo examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls. MATERIALS &

methodsNext-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.

results12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.

conclusionsGenetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.

Indexed as

AdultAgedAged, 80 and overCalcium ChannelsCalcium Channels, L-TypeCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenetic VariationHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedMuscular DiseasesRetrospective StudiesRyanodine Receptor Calcium Release ChannelCACNA1S protein, humanCalcium ChannelsCalcium Channels, L-TypeHydroxymethylglutaryl-CoA Reductase InhibitorsRyanodine Receptor Calcium Release ChannelRYR1 protein, humanexome sequencingmalignant hyperthermiamyopathyRYR1statin

Identifiers

PMID30325262
PMCPMC6563124

What OpenQuestion holds

Textmetadata
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.