Test Code SLC1Q Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Varies
Ordering Guidance
Testing is available as the single gene assay (this test) or as a part of a focused pharmacogenomics panel, which includes testing for the following genes: CYPs 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4F2, SLCO1B1, and VKORC1. Order PGXQP / Focused Pharmacogenomics Panel, Varies if multiple pharmacogenomic genotype testing is desired.
Specimen Required
Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List for a list of tests that can be ordered together.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Specimen Type: Extracted DNA
Container/Tube: 2 mL screw top tube
Specimen Volume: 100 mcL (microliters)
Collection Instructions:
1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Useful For
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
This is a pharmacogenomic test for genotype for the rs4149056 (c.521T>C) variant found in the *5 allele. Presence of the *5 allele is associated with an increased risk for simvastatin-associated myopathy.
Special Instructions
Method Name
Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis
Reporting Name
SLCO1B1 Genotype, VSpecimen Type
VariesSpecimen Minimum Volume
Blood: 0.4 mL
Saliva: 1 swab
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
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)
Frequency of the SLCO1B1 alleles varies across different racial and ethnic groups.
Reference Values
An interpretive report will be provided.
Interpretation
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. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.
Cautions
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.
Specimens may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from specimens 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.
Method Description
Genomic DNA is extracted from whole blood or saliva. Genotyping for SLCO1B1 alleles is performed using a polymerase chain reaction (PCR)-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. A genotype is assigned based on the allele-specific fluorescent signals that are detected.(Unpublished Mayo method)
Day(s) Performed
Monday through Friday
Report Available
3 to 8 daysPerforming Laboratory
Mayo Clinic Laboratories in RochesterTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81328
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
SLC1Q | SLCO1B1 Genotype, V | 93412-5 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
610152 | SLCO1B1 Genotype | 93412-5 |
610153 | SLCO1B1 Phenotype | 79722-5 |
610154 | Interpretation | 69047-9 |
610155 | Additional Information | 48767-8 |
610156 | Method | 85069-3 |
610157 | Disclaimer | 62364-5 |
610158 | Reviewed by | 18771-6 |