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.

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Keywords atorvastatin, ATP-binding cassette sub-family C member 2, multidrug resistance-associated protein 2, pharmacogenetics, Simvastatin
Persistent URL dx.doi.org/10.1038/tpj.2011.59, hdl.handle.net/1765/65978
Journal The Pharmacogenomics Journal
Citation
Becker, M.L, Elens, L, Visser, L.E, Hofman, A, Uitterlinden, A.G, van Schaik, R.H.N, & Stricker, B.H.Ch. (2013). Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. The Pharmacogenomics Journal, 13(3), 251–256. doi:10.1038/tpj.2011.59