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Test ID: SLC1B Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Blood

Reporting Name

SLCO1B1 Genotype, Statin, B

Useful For

Aiding risk prediction for statin-associated myopathy in patients beginning statin therapy, especially simvastatin therapy, in whole blood specimens

 

Determining a potential genetic effect related to statin intolerance in patients with statin-associated myopathy, especially related to simvastatin

Specimen Type

Whole Blood EDTA


Specimen Required


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.


Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood EDTA Ambient (preferred)
  Refrigerated 

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Tuesday; time varies

Test Classification

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

81400-SLCO1B1 (solute carrier organic anion transporter family, member 1B1) (eg, adverse drug reaction), V174A variant

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SLC1B SLCO1B1 Genotype, Statin, B In Process

 

Result ID Test Result Name Result LOINC Value
34695 SLCO1B1 Genotype Result In Process
34696 SLCO1B1 Interpretation 79722-5
34697 Reviewed by No LOINC Needed

Clinical Information

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.

Interpretation

Heterozygosity and homozygosity for the SLCO1B1*5 allele is associated with decreased organic anion-transporting polypeptide 1B1 (OATP1B1) activity and an increased risk for simvastatin-associated myopathy.

 

Absence of the SLCO1B1*5 allele decreases, but does not rule out the risk of simvastatin-associated myopathy. For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Clinical Reference

1. 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 Oct;96(4):423-428

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

Analytic Time

1 day (Not reported on Saturday or Sunday)

Method Name

Polymerase Chain Reaction (PCR) 5'-Nuclease End-Point Allelic Discrimination Analysis

Forms

1. 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 (T576) is available in Special Instructions.

2. If not ordering electronically, complete, print, and send a Cardiovascular Test Request Form (T724) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/cardiovascular-request-form.pdf).

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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