Simvastatin (Zocor) – SLCO1B1
Rationale
This drug gene interaction (DGI) pertains to the interaction between the SLCO1B1 gene and simvastatin. Simvastatin belongs to a group of drugs called statins. Simvastatin works by inhibiting an enzyme called HMG CoA reductase that the liver uses to make cholesterol. Thus, simvastatin reduces blood cholesterol and helps prevent atherosclerosis (heart disease). Extensive literature indicates patients with specific genetic differences in the SLCO1B1 gene may have increased levels of simvastatin and increased risk of muscle related side effects.
Information presented on this page is based on evidence provided by the Clinical Pharmacogenomics Implementation Consortium (CPIC®). CPIC provides peer-reviewed, updated, evidence-based, and freely accessible guidelines for implementing pharmacogenomic results into actionable prescribing decisions for providers. CPIC guidelines include standardized terminology and a systematic grading of evidence and clinical recommendations published in a leading journal (Clinical Pharmacology and Therapeutics).
Genetic Variant Information
The SLCO1B1 gene encodes the solute carrier organic anion transporter family member 1b1 (SLCO1B1), which is a transporter protein that helps the body get rid of certain medications through the liver. There are different (variant) forms of the SLCO1B1 gene, or alleles, and differences ultimately affect how well simvastatin is metabolized in the body. Some variants encode normal functioning transporter proteins while others encode decreased or poor functioning transporter proteins. Each of us carry two alleles of this gene. Assessing both alleles give a better picture of the functional status or phenotype of how statins are metabolized. See the chart below for a description of each phenotype and any implications for treatment.
SLCO1B1 Phenotype |
Variants (genotype) |
Implication for simvastatin* |
|---|---|---|
| Poor function | TWO no function alleles | Highly increased risk of SAMS |
| Decreased function | ONE normal function allele AND ONE no function allele | Increased risk of SAMS |
| Normal function | TWO normal function alleles | No increased risk of SAMS |
*Statin-associated muscle symptoms (SAMS) risk can include myopathy, myalgia, or weakness.
Limited pediatric evidence for simvastatin.
The patient’s reported genotype corresponds to a phenotype. To see an interpretation table assigning functional status by genotype, click here to visit CPIC and scroll down to click and download “SLCO1B1 diplotype-phenotype table”.
Results Interpretation
Simvastatin is a medicine used to manage several different conditions and your genes can affect how well the drug works. CPIC updates guidelines on how to best use these genetic results to support patient care. To view dosing recommendations for statins based on SLCO1B1 phenotypes, click on the most recent guideline publication on CPIC’s website and scroll down to Table 2.
Please review the FDA packet insert for additional clinical considerations such as contradictions as well as dose adjustments based on age, organ function, and drug-drug interactions.
Quality of Results
Genotyping for SCLO1B1 was performed within a certified DNA laboratory at Vanderbilt University Medical Center that is in full compliance with all guidelines established by the government as regulated by the Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Act of 1988. This validated clinical laboratory developed test is carried out with strict adherence to protocols outlined by the College of American Pathology. The performance of the assay is closely monitored and the accuracy of the results is determined to be > 99%.
Supporting Evidence
This link will take you to the main page on the CPIC website relating to SCLO1B1 and simvastatin. On the site, you will find links to the main guideline publication and all supplementary information including a table that reports variant frequencies across different races/ethnic groups, a table that defines genetic variants, and a table that provides a phenotype interpretation (i.e. metabolizer status). Additionally, examples of point of care clinical decision support can be found at the bottom of the page.