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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 volume 13, pages 251–256 (2013)Cite this article

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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.

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Authors and Affiliations

  1. Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

    M L Becker, L E Visser, A Hofman, A G Uitterlinden & B H Stricker

  2. Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands

    M L Becker & L E Visser

  3. Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands

    L L F S Elens & R H N van Schaik

  4. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

    L E Visser, A G Uitterlinden & B H Stricker

  5. STAR Medical Diagnostic Center, Rotterdam, The Netherlands

    R H N van Schaik

  6. Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands

    B H Stricker

  7. Drug Safety Unit, Inspectorate for Health Care, The Hague, The Netherlands

    B H Stricker

Authors
  1. M L Becker
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  2. L L F S Elens
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  3. L E Visser
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  4. A Hofman
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  5. A G Uitterlinden
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  6. R H N van Schaik
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  7. B H Stricker
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Correspondence to B H Stricker.

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Becker, M., Elens, L., Visser, L. et al. 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 13, 251–256 (2013). https://doi.org/10.1038/tpj.2011.59

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  • DOI: https://doi.org/10.1038/tpj.2011.59

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