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Test Catalog

Test ID: SLC1Q    
Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Predicting risk for statin-associated myopathy in patients beginning statin therapy, especially simvastatin therapy

 

Determining a potential statin lipid lowering response, especially when using pravastatin

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This is a pharmacogenomics test for genotype for the rs4149056 (c.521T>C) variant found in the *5, *15, and *17 alleles, and rs4149015 (c.-910G>A) found in the *17 and *21 alleles. Presence of the *5 allele is associated with an increased risk for simvastatin-associated myopathy.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The most common adverse drug reaction associated with statins is skeletal muscle toxicity, which can include myalgia (with and without elevated creatine kinase levels), muscle weakness, muscle cramps, myositis, and rhabdomyolysis.(1) Rhabdomyolysis, while rare, is of clinical concern because of the risk for death as a result of cardiac arrhythmia, renal failure, and disseminated intravascular coagulation. While the underlying causes of statin-associated myopathy are not known, several hypotheses have been formulated, including those related to the biochemical pathway of cholesterol synthesis inhibition and statin metabolism.

 

SLCO1B1 encodes the organic anion-transporting polypeptide 1B1 (OATP1B1) influx transporter located on the basolateral membrane of hepatocytes. OATP1B1 facilitates the hepatic uptake of statins as well as other endogenous compounds (eg, bilirubin). Changes in the activity of this transporter (eg, through genetic variations or drug-drug interactions) can increase the severity of statin-associated myopathy (ie, statin intolerance).(2)

 

SLCO1B1 rs4149056 (c.521T>C, p.V174A), which is found in *5, *15, and *17, interferes with localization of the transporter to the plasma membrane and can lead to increased systemic statin concentrations.(3-4) All statins are substrates of OATP1B1, but the association of SLCO1B1 c.521T>C with statin intolerance varies depending on statin and dose and is most pronounced with higher doses of simvastatin therapy. A case-control study of simvastatin-induced myopathy observed an odds ratio (OR) for myopathy of 4.5 for *5 heterozygotes and 16.9 for *5 homozygotes (compared to individuals who did not carry *5) among patients receiving high-dose (80 mg/day) simvastatin therapy.(4) A dose relationship was also demonstrated in a replication cohort of patients taking 40 mg/day simvastatin with a relative risk of 2.6 per copy of the *5 allele. While the SLCO1B1 c.521T>C genotype has also been shown to affect systemic exposure of other statins (eg, atorvastatin, pravastatin, rosuvastatin) in addition to simvastatin,(3) there is less evidence demonstrating a clinical association between the SLCO1B1 genotype and myopathy with statins other than simvastatin.(2)

 

SLCO1B1 rs4149015 (c.-910G>A), which is found in *17 and *21, is associated with increased pravastatin blood levels and a reduced lipid lowering effect but has not been associated with statin-induced myopathy or rhabdomyolysis. 

 

Frequency of the SLCO1B1 alleles varies across different racial and ethnic groups.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided. The complementary DNA positions are based on NM_006446.4.

 

For additional information regarding pharmacogenomic genes and their associated drugs, see Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Rare variants may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings (phenotype), additional testing should be considered.

 

Samples may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing. SLCO1B1 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's SLCO1B1 status.

 

Simvastatin-related myopathy can occur in the absence of SLCO1B1 c.521T>C.

 

The presence of SLCO1B1 c.521T>C does not confer absolute risk for simvastatin-associated myopathy.

 

Absence of a variant allele does not rule out the possibility that a patient harbors another variant that can impact medication efficacy and side effects.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Wilke RA, Lin DW, Roden DM, et al: Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges [published correction appears in Nat Rev Drug Discov. 2008 Feb;7(2):185]. Nat Rev Drug Discov. 2007;6(11):904-916. doi: 10.1038/nrd2423

2. Ramsey LB, Johnson SG, Caudle KE, et al: The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014;96(4):423-428. doi: 10.1038/clpt.2014.125

3. Niemi M. Transporter pharmacogenetics and statin toxicity: Clin Pharmacol Ther. 2010;87(1):130-133. doi: 10.1038/clpt.2009.197

4. SEARCH Collaborative Group, Link E, Parish S, et al: SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008;359(8):789-799. doi: 10.1056/NEJMoa0801936

Special Instructions Library of PDFs including pertinent information and forms related to the test