Evidence map›Paper›PMID 34668025›Full record

ArticleEuropean journal of clinical pharmacology2022

Loss of function polymorphisms in SLCO1B1 (c.521T>C, rs4149056) and ABCG2 (c.421C>A, rs2231142) genes are associated with adverse events of rosuvastatin: a case-control study.

Iveta Merćep, Ivana Radman, Vladimir Trkulja, Tamara Božina, Livija Šimičević, Ema Budimir, Lana Ganoci, Nada Božina

Abstract read
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In one paragraph

Article in European journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 4 pooled it
1.2field-weighted citation impact, top 18% 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

12 citing papers in PubMed, 4 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
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  5. Review
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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

8 authors at 2 institutions in 1 country.

Iveta MerćepDepartment of Internal Medicine, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.ORCID http://orcid.org/0000-0003-2824-9222
Ivana RadmanUniversity Department of Ophthalmology, University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia.ORCID http://orcid.org/0000-0001-7912-6017
Vladimir TrkuljaDepartment of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.ORCID http://orcid.org/0000-0002-0968-1194
Tamara BožinaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, Croatia.ORCID http://orcid.org/0000-0001-5883-7979
Livija ŠimičevićDivision of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.ORCID http://orcid.org/0000-0002-2491-1920
Ema BudimirUniversity of Zagreb School of Medicine, Zagreb, Croatia.ORCID http://orcid.org/0000-0001-7937-7019
Lana GanociDivision of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.ORCID http://orcid.org/0000-0003-3898-4554
Nada BožinaDepartment of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia. nada.bozina@mef.hr.ORCID http://orcid.org/0000-0001-6016-1699
University Hospital Centre Zagreb · HRUniversity of Zagreb · HR

Funding

sveučilište u zagrebu UniZG2018
6 · The paper itself

Abstract

purposeThe study aims to evaluate relationship between polymorphisms associated with a reduced function of two transporter proteins resulting in increased exposure to rosuvastatin - organic anion transporter 1B1 (OATP1B1) (SLCO1B1 c.521T>C) and ATP binding cassette subfamily G member 2 (ABCG2) (ABCG2 c.421C>A) and occurrence of rosuvastatin related myotoxicity/hepatotoxicity.

methodsIn a case-control study, cases (rosuvastatin treated patients developing myotoxicity or hepatotoxicity) and controls (concurrent rosuvastatin treated patients free of adverse events) were prospectively recruited over a 2 year period in a single tertiary center specialized in treatment of metabolic disorders. Subjects were evaluated for clinical, comorbidity, and comedication characteristics and for genotype predicted metabolizing phenotypes regarding cytochrome P450 enzymes CYP2C9 and CYP2C19. Standard regression analysis and analysis in matched sets of cases and controls (optimal full matching) were undertaken by fitting frequentist and Bayesian models (covariates/matching variables: age, sex, diabetes, liver/renal disease, hypertension, CYP2C9 and C19 phenotype, use of CYP or transporter inhibitors, non evaluated transporter genotype).

resultsA total of 88 cases (81 with myotoxicity, 6 with hepatotoxicity, 1 with both) and 129 controls were recruited. Odds of variant SLCO1B1 c.521T>C allele were 2.2-2.5 times higher in cases than in controls (OR = 2.45, 95% CI 1.34-4.48; Bayesian OR = 2.59, 95% CrI 1.42-4.90 in regression analysis; OR = 2.20, 1.10-4.42; Bayesian OR = 2.26, 1.28-4.41 in matched analysis). Odds of variant ABCG2 c.421C>A allele were 2.1-2.3 times higher in cases than in controls (OR = 2.24, 1.04-4.83; Bayesian OR = 2.35, 1.09-4.31 in regression analysis; OR = 2.10, 0.83-5.31; Bayesian OR = 2.17, 1.07-4.35 in matched analysis).

conclusionLoss of function polymorphisms in SLCO1B1 c.521T>C and ABCG2 c.421C>A genes are associated with the presence of rosuvastatin related myotoxicity and/or hepatotoxicity.

Indexed as

AgedAge FactorsATP Binding Cassette Transporter, Subfamily G, Member 2Bayes TheoremCase-Control StudiesChemical and Drug Induced Liver InjuryComorbidityCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Dose-Response Relationship, DrugFemaleGenotypeHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLiver-Specific Organic Anion Transporter 1MaleABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Hydroxymethylglutaryl-CoA Reductase InhibitorsLiver-Specific Organic Anion Transporter 1Neoplasm ProteinsRosuvastatin CalciumSLCO1B1 protein, humanABCG2HepatotoxicityMyotoxicityPolymorphismRosuvastatinSLCO1B1

Identifiers

PMID34668025
OpenAlexW3207565547

What OpenQuestion holds

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Registered trials

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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.