Journal
PHARMACOGENETICS AND GENOMICS
Volume 24, Issue 1, Pages 43-51Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0000000000000018
Keywords
adverse drug reaction; atorvastatin; c; 521T > C; pharmacogenetics; simvastatin; SLCO1B1
Funding
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) [050-060-810]
- Erasmus Medical Center
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly
- Ministry of Education, Culture, and Science
- Ministry of Health Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Dutch Health Insurance Board (CVZ)
- Royal Dutch Association for the Advancement of Pharmacy (KNMP)
- Top Institute Pharma
- EU Innovative Medicines Initiative (IMI)
- EU
- Dutch Medicines Evaluation Board
- Dutch Ministry of Health and Industry, GlaxoSmithKline
- Dutch Ministry of Health and Industry, Pfizer
Ask authors/readers for more resources
ObjectiveThe 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.Materials and methodsWe 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.ResultsSimvastatin 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.ConclusionIn 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available