Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy.
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Becker ML, Elens LL, Visser LE, Hofman A, Uitterlinden AG, van Schaik RH, Stricker BH
Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy.
Pharmacogenomics J. 2013 Jun;13(3):251-6. doi: 10.1038/tpj.2011.59. Epub 2011 Dec 20.
- PubMed ID
- 22186618 [ View in PubMed]
- Abstract
Several statins are substrates for the multidrug resistance-associated protein 2 transporter, encoded by the ABCC2 gene. We analyzed in the Rotterdam Study whether the common polymorphisms -24C>T, 1249G>A and 3972C>T in the ABCC2 gene were associated with a dose decrease or switch to another cholesterol-lowering drug in simvastatin and atorvastatin users. These events could indicate an adverse effect or a too strong reduction in cholesterol level. We identified 1014 simvastatin and atorvastatin users during the period 1 January 1991 to 1 January 2010. Associations between genetic variation and the risk of these events were analyzed using Cox proportional hazards modelling. The ABCC2 -24C>T genotype (HR 1.32 95% CI 1.04-1.69) and the H12 haplotype versus the H2 haplotype (HR 1.49; 95% CI 1.06-2.09) were associated with these events in simvastatin users. A similar but not significant association was found in atorvastatin users. To conclude, genetic variation in the ABCC2 gene is associated with these events in simvastatin users.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Atorvastatin Canalicular multispecific organic anion transporter 1 Protein Humans NoSubstrateDetails Simvastatin Canalicular multispecific organic anion transporter 1 Protein Humans UnknownSubstrateDetails