Real-world pharmacogenetics of statin intolerance: effects of SLCO1B1, ABCG2 , and CYP2C9 variants.
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ adverse effects
Atorvastatin
/ adverse effects
Rosuvastatin Calcium
/ adverse effects
Pravastatin
/ adverse effects
Cytochrome P-450 CYP2C9
/ genetics
Fluvastatin
/ adverse effects
Pharmacogenetics
Simvastatin
/ adverse effects
Liver-Specific Organic Anion Transporter 1
/ genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ genetics
Neoplasm Proteins
/ genetics
Journal
Pharmacogenetics and genomics
ISSN: 1744-6880
Titre abrégé: Pharmacogenet Genomics
Pays: United States
ID NLM: 101231005
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
medline:
10
8
2023
pubmed:
25
7
2023
entrez:
25
7
2023
Statut:
ppublish
Résumé
The association of SLCO1B1 c.521T>C with simvastatin-induced muscle toxicity is well characterized. However, different statins are subject to metabolism and transport also by other proteins exhibiting clinically meaningful genetic variation. Our aim was to investigate associations of SLCO1B1 c.521T>C with intolerance to atorvastatin, fluvastatin, pravastatin, rosuvastatin, or simvastatin, those of ABCG2 c.421C>A with intolerance to atorvastatin, fluvastatin, or rosuvastatin, and that of CYP2C9*2 and *3 alleles with intolerance to fluvastatin. We studied the associations of these variants with statin intolerance in 2042 patients initiating statin therapy by combining genetic data from samples from the Helsinki Biobank to clinical chemistry and statin purchase data. We confirmed the association of SLCO1B1 c.521C/C genotype with simvastatin intolerance both by using phenotype of switching initial statin to another as a marker of statin intolerance [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.08-3.25, P = 0.025] and statin switching along with creatine kinase measurement (HR 5.44, 95% CI 1.49-19.9, P = 0.011). No significant association was observed with atorvastatin and rosuvastatin. The sample sizes for fluvastatin and pravastatin were relatively small, but SLCO1B1 c.521T>C carriers had an increased risk of pravastatin intolerance defined by statin switching when compared to homozygous reference T/T genotype (HR 2.11, 95% CI 1.01-4.39, P = 0.047). The current results can inform pharmacogenetic statin prescribing guidelines and show feasibility for the methodology to be used in larger future studies.
Identifiants
pubmed: 37490620
doi: 10.1097/FPC.0000000000000504
pii: 01213011-990000000-00033
pmc: PMC10399933
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Atorvastatin
A0JWA85V8F
Rosuvastatin Calcium
83MVU38M7Q
Pravastatin
KXO2KT9N0G
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Fluvastatin
4L066368AS
Simvastatin
AGG2FN16EV
CYP2C9 protein, human
EC 1.14.13.-
SLCO1B1 protein, human
0
Liver-Specific Organic Anion Transporter 1
0
ABCG2 protein, human
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
153-160Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
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