This DGI pertains to the interaction between the SLCO1B1 gene and simvastatin. Simvastatin works by inhibiting an enzyme called HMG CoA reductase that the liver uses to make cholesterol. Thus, simvastatin reduces blood cholesterol and helps to prevent atherosclerosis (heart disease). Extensive literature indicates patients with a specific alteration in SLCO1B1 (rs4149056T>C) will experience increase systemic exposure to simvastatin and risk muscle toxicity.
Information presented on this page is based on evidence provided by the Clinical Pharmacogenomics Implementation Consortium (CPIC®). One goal of CPIC is to provide peer-reviewed, updated, evidence-based, and freely accessible guidelines for implementing the use of pharmacogenomic tests into actionable prescribing decisions for patient care. CPIC guidelines follow standardized formats, include systematic grading of evidence and clinical recommendations, use standardized terminology, are peer-reviewed, and are published in a leading journal (in partnership with Clinical Pharmacology and Therapeutics) with simultaneous posting to cpicpgx.org, where they are regularly updated.
The SLCO1B1 gene encodes the solute carrier organic anion transporter family member 1b1 (SLCO1B1) enzyme, which is a drug transporter that helps the body get rid of certain medications through the liver. There are different SLCO1B1 gene versions, or variants, and each has a different effect on how well simvastatin is metabolized in the body. Some variants result in normal function while others function only at an intermediate or low level. See chart below for a description of each phenotype and any implications for treatment.
Patient’s genetic information is reported as a diplotype and this corresponds to a phenotype (i.e. risk). To see an interpretation table assigning functional status by genetic variant, click here to visit CPIC and scroll down to click and download “SLCO1B1 diplotype-phenotype table”. A results interpretation by metabolizer status is located below.
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%.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for SLCO1B1 and Simvastatin-Induced Myopathy: 2014 Update
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.