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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.

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Becker, M L Elens, Laure [UCL] Visser, L E Hofman, A Uitterlinden, A G Stricker, B H

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.

Document type Article de périodique (Journal article)
Publication date 2013
Language Anglais
Journal information "The Pharmacogenomics Journal" - Vol. 13, no.3, p. 251-256 (2011)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 1470-269X
e-issn 1473-1150
Affiliation UCL - SSS/LDRI - Louvain Drug Research Institute
MESH Subject Aged ; Humans ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Pyrroles ; Simvastatin ; Anticholesteremic Agents ; Cholesterol ; Dose-Response Relationship, Drug ; Drug-Related Side Effects and Adverse Reactions ; Female ; Genetic Association Studies ; Haplotypes ; Heptanoic Acids
Links
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Bibliographic reference Becker, M L ; Elens, Laure ; Visser, L E ; Hofman, A ; Uitterlinden, A G ; 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.. In: The Pharmacogenomics Journal, Vol. 13, no.3, p. 251-256 (2011)
Permanent URL http://hdl.handle.net/2078.1/161651