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The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study.

Authors :
de Keyser CE
Peters BJ
Becker ML
Visser LE
Uitterlinden AG
Klungel OH
Verstuyft C
Hofman A
Maitland-van der Zee AH
Stricker BH
Source :
Pharmacogenetics and genomics [Pharmacogenet Genomics] 2014 Jan; Vol. 24 (1), pp. 43-51.
Publication Year :
2014

Abstract

Objective: The SLCO1B1 c.521T>C polymorphism is associated with statin plasma levels and simvastatin-induced adverse drug reactions. We studied whether the c.521T>C polymorphism is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy, because these events are indicators of adverse drug reactions.<br />Materials and Methods: We identified 1939 incident simvastatin and atorvastatin users in the Rotterdam Study, a population-based cohort study. Associations were studied using Cox proportional hazards analysis. Meta-analysis was performed with data from the Utrecht Cardiovascular Pharmacogenetics study.<br />Results: Simvastatin users with the c.521 CC genotype had a significantly higher risk of a dose decrease or switch than users with the TT genotype [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.05-2.88]. Female sex, age below 70 years, and low starting dose were risk factors. In atorvastatin users with starting dose of more than 20 mg, the risk of a dose decrease or switch was higher in users carrying a C allele than in users with the TT genotype (HR 3.26, 95% CI 1.47-7.25). In the meta-analysis the association in simvastatin users remained, with a significantly higher risk of a dose decrease or switch in simvastatin users with two minor alleles (HR 1.69, 95% CI 1.05-2.73). For atorvastatin users no significant association was found.<br />Conclusion: In simvastatin users in the Rotterdam Study, we demonstrated an association between the c.521T>C polymorphism and dose decrease or switching, as indicators of adverse drug reactions, and provided risk factors for this association. For atorvastatin, an association was found in users with a starting dose of more than 20 mg.

Details

Language :
English
ISSN :
1744-6880
Volume :
24
Issue :
1
Database :
MEDLINE
Journal :
Pharmacogenetics and genomics
Publication Type :
Academic Journal
Accession number :
24263182
Full Text :
https://doi.org/10.1097/FPC.0000000000000018