Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) Genotype, Statin, Blood
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.
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
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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Blood samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow 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 blood or marrow 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.
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 variants 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.
Rare variants 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.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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