Impact of genetic variation on response to therapy
The SLCO1B1 transporter (also known as OATP1B1 and OATP-C) plays an important role in the transfer of statins from the blood into the liver. Reduced function of this transporter can lead to increased plasma concentrations of statins and potentially an increased risk of statin-related muscle toxicity (SRM) including myopathy and rhabdomyolysis.
Many variants have been found in the SLCO1B1 gene. The variant c.521T>C is a loss-of-function variant, which has been found to be associated with an increased risk of SRM. The c.521T>C variant is contained within the SLCO1B1*5 and *15 allele haplotypes.
The SmPC for atorvastatin states that being a homozygous C/C carrier of c.521T>C is associated with a 2.4-fold higher atorvastatin exposure compared to people with the genotype T/T. The SmPC provides a special warning and precaution for use that atorvastatin should be prescribed with caution in patients with pre-disposing risk factors for rhabdomyolysis including those with loss-of-function variants in the SLCO1B1 gene.
The main benefit of pharmacogenomic testing for atorvastatin is to identify patients who have a higher potential to experience SRM and to aid drug choice and dose modification.
Testing recommendations
At the time of publication there are no UK recommendations for SLCO1B1 testing to guide the use of atorvastatin.
Therapeutic recommendations
SLCO1B1 status unknown
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 increased function
Some examples of SLCO1B1 genotypes include (see note): *14/*14
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 normal function
Some examples of SLCO1B1 genotypes include (see note): *1/*1, *1/*14, c.521T/T
- Initiate and titrate according to disease-specific guidelines.
SLCO1B1 decreased function
Some examples of SLCO1B1 genotypes include (see note): *1/*5, *1/*15, c.521T/C
- Increased plasma levels compared to individuals with SLCO1B1 normal function.
- Initiate and titrate according to disease specific guidelines.
- Be aware that higher doses are associated with increased risk of SRM, especially for doses ≥40mg daily. If >40mg daily is required, consider combination therapy with a non-statin cholesterol lowering agent.
- If patient has additional risk factors for SRM, consider an alternative statin if clinically appropriate (see Further information), or keep the dose as low as possible (e.g. by adding non-statin cholesterol lowering agent).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
SLCO1B1 poor function
Some examples of SLCO1B1 genotypes include (see note): *5/*5, *5/*15, *15/*15, c.521C/C
- Increased plasma levels compared to individuals with SLCO1B1 normal or decreased function.
- Initiate with ≤20mg daily and titrate according to disease specific guidelines.
- Be aware that higher doses are associated with increased risk of SRM, especially for doses ≥20mg daily. If >20mg daily is required, consider combination therapy with a non- statin cholesterol lowering agent.
- If patient has additional risk factors for SRM, consider an alternative statin if clinically appropriate (see Further information), or keep the dose as low as possible (e.g. by adding non-statin cholesterol lowering agent).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
Note: Both the star(*) allele and c.521T>C genotype are provided as examples. Reporting methodology may vary by laboratory.
Further information
Drug interactions
The effects of drug-drug interactions with atorvastatin may be more pronounced in people with reduced SLCO1B1 function and are likely to be additive to the impact of genetic variation. Multiple mechanisms may contribute to potential interactions with statins. Drugs, herbal products or other substances that inhibit certain enzymes (e.g. CYP3A4) and/or transporter pathways (e.g. SLCO1B1, P-Glycoprotein, BCRP) may increase atorvastatin plasma concentrations and may lead to an increased risk of myopathy or rhabdomyolysis. Consult the SmPC of atorvastatin and of all concomitantly used drugs to obtain further information about their potential interactions with atorvastatin.
Other factors influencing risk of SRM
The risk of SRM is influenced by a variety of factors in addition to genotype. These include dose, age, gender, comorbidities and drug interactions. Additional risk factors for SRM should be considered when prescribing statins.
Patients already on stable and effective statin therapy
The main benefit of pharmacogenomic testing for statins is to aid in medication selection by identifying patients who are more or less likely to experience adverse effects including SRM. For patients who have already been on a stable and effective statin dose for more than 1 year without concerns regarding adverse effects, it is likely to be safe to continue.
Other genes associated with clinical response to atorvastatin
Other genes associated with clinical response to atorvastatin include ABCG2, CYP3A4 and CYP3A5. However, there is currently insufficient evidence to provide therapeutic recommendations for atorvastatin based on ABCG2, CYP3A4 or CYP3A5 genotype.
Alternative statins in individuals with reduced SLCO1B1 function
Rosuvastatin and pravastatin are influenced to a similar extent by SLCO1B1 variation and have less drug interactions with 3A4 inhibitors. Fluvastatin is influenced to a lesser extent by SLCO1B1 variation. See individual drug monographs for further information. Choice of statin should consider lipid lowering intensity, and local and national statin prescribing guidelines.
References
Clinical Pharmacogenetics Implementation Consortium CPIC® (2022) Guideline for statins and SLCO1B1, ABCG2, and CYP2C9. Available at: https://www.clinpgx.org/guideline/PA166264281
Viatris (2025) Lipitor 40mg Tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/5238/smpc (Accessed online: 23/2/2026).
Wolthuis et al. (2025). Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas. European Journal of Human Genetics, 33(4):413-420. https://doi.org/10.1038/s41431-024-01769-7 Accessed online 12/2/2026.
NHS England (2023) Statin intolerance pathway. Available at: https://www.england.nhs.uk/aac/publication/statin-intolerance-pathway/ Accessed online 27th May 2026.
