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.
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ genetics
Age Factors
Aged
Bayes Theorem
Case-Control Studies
Chemical and Drug Induced Liver Injury
/ genetics
Comorbidity
Cytochrome P-450 CYP2C19
/ genetics
Cytochrome P-450 CYP2C9
/ genetics
Dose-Response Relationship, Drug
Female
Genotype
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ adverse effects
Liver-Specific Organic Anion Transporter 1
/ genetics
Male
Middle Aged
Myotoxicity
/ genetics
Neoplasm Proteins
/ genetics
Phenotype
Polymorphism, Single Nucleotide
Rosuvastatin Calcium
/ adverse effects
Sex Factors
ABCG2
Hepatotoxicity
Myotoxicity
Polymorphism
Rosuvastatin
SLCO1B1
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
23
06
2021
accepted:
11
10
2021
pubmed:
21
10
2021
medline:
26
2
2022
entrez:
20
10
2021
Statut:
ppublish
Résumé
The 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. In 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). A 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). Loss 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.
Identifiants
pubmed: 34668025
doi: 10.1007/s00228-021-03233-7
pii: 10.1007/s00228-021-03233-7
doi:
Substances chimiques
ABCG2 protein, human
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Liver-Specific Organic Anion Transporter 1
0
Neoplasm Proteins
0
SLCO1B1 protein, human
0
Rosuvastatin Calcium
83MVU38M7Q
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
227-236Subventions
Organisme : sveučilište u zagrebu
ID : UniZG2018
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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