SLCO1B1
Solute carrier organic anion transporter family member 1B1 (Liver-specific organic anion transporter 1) (LST-1) (OATP-C) (Sodium-independent organic anion-transporting polypeptide 2) (OATP-2) (Solute carrier family 21 member 6) [LST1] [OATP1B1] [OATP2] [OATPC] [SLC21A6]
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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. 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. 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. 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.
MeSH Terms
- Aged
- Aging
- Anticholesteremic Agents
- Atorvastatin
- Cholesterol
- Cytosine
- Databases, Factual
- Dose-Response Relationship, Drug
- Female
- Genetic Association Studies
- Heptanoic Acids
- Humans
- Hypercholesterolemia
- Liver-Specific Organic Anion Transporter 1
- Male
- Middle Aged
- Organic Anion Transporters
- Polymorphism, Single Nucleotide
- Prospective Studies
- Pyrroles
- Risk Factors
- Sex Characteristics
- Simvastatin
- Thymine