Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Aiding prediction of risk for statin-associated myopathy in patients beginning statin therapy, especially simvastatin therapy
Determining a potential genetic effect related to statin intolerance in patients with statin-associated myopathy, especially related to simvastatin
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase chain reaction (PCR) 5'-Nuclease End-Point Allelic Discrimination Analysis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
SLCO1B1 Genotype, Statin, B
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
Additional Information: Patients who had a heterologous blood transfusion within the preceding 45 days (6 weeks), or who have received an allogeneic bone marrow transplant, can have false genetic test results as human DNA present in the blood may be a mixture of patient and donor DNA. For these patients, saliva specimen (rather than blood) should be submitted, order SLC1O/61737 Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Saliva.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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).(1)
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.(2) 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.
The SLCO1B1 *5 (c.521T->C, p.V174A; rs4149056) allele interferes with localization of the transporter to the plasma membrane, and can lead to increased systemic statin concentrations.(3) All statins are substrates of OATP1B1, but the association with SLCO1B1 *5 and 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 per copy of the *5 allele in patients receiving high-dose (80 mg/day) simvastatin therapy (the OR was 16.9 in *5 homozygotes compared to individuals who did not carry *5).(4) Also demonstrated was a dose relationship 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 SLCO1B1 genotype has 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 SLCO1B1 genotype and myopathy with statins other than simvastatin.(1)
Frequency of the SLCO1B1 *5 allele varies across different racial and ethnic groups. The *5 allele occurs in the homozygous or heterozygous state in approximately 20% to 28% of Caucasians and Asians, and 8% of Africans.
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.
Heterozygosity and homozygosity for the SLCO1B1 *5 allele is associated with decreased OATP1B1 activity and an increased risk for simvastatin-associated myopathy.
Absence of the SLCO1B1 *5 allele decreases, but does not rule-out entirely, the risk of simvastatin-associated myopathy.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test may not be useful for patients taking a statin other than simvastatin.
Simvastatin-related myopathy can occur in the absence of SLCO1B1 *5.
The presence of SLCO1B1 *5 does not confer absolute risk for simvastatin-associated myopathy.
This test does not detect polymorphism or mutations other than the specific *5 allele in exon 6.
This test is not indicated for stand-alone diagnostic purposes.
This test is not intended to be used to predict drug response.
Drug-drug interactions and drug/metabolite inhibition must be considered.
Blood transfusions or bone marrow transplantation prior to having blood drawn for DNA analysis can generate false results as DNA in the specimen may be a mix of patient and donor DNA. Alternative saliva specimen type can be ordered as SLC1O/61737 Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Saliva.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing could be considered.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Wilke RA, Ramsey LB, Johnson SG, et al: The Clinical pharmacogenomics Implementation Consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther 2012. Epub ahead of print
2. Wilke RA, Lin DW, Roden DM, et al: Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov 2007;6(11):904-916
3. Niemi M: Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 2012;87:130-133
4. Link E, Parish S, Armitage J, et al: SLCO1B1 variants and statin-induced myopathy-a genomewide study. N Engl J Med 2008 Aug 21;359(8):789-799
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. Genotyping for the SLCO1B1*5 allele is performed using a 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 *5 allele. 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.(Package insert: Taqman SNP Genotyping Assay, Applied Biosystems. rev D 07/2010)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks; Extracted DNA: 2 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479 -Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|34695||SLCO1B1 Genotype Result||N/A|