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. The ABCG2 (also known as BCRP) transporter is expressed in many different tissues and facilitates the export of compounds into the extracellular space. Reduced function of either transporters can lead to increased plasma concentrations of rosuvastatin 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 increased plasma concentrations of rosuvastatin. The c.521T>C variant is contained within the SLCO1B1*5 and *15 allele haplotypes.
The ABCG2 gene variant c.421C>A is a loss-of-function variant, which has been associated with increased plasma levels of rosuvastatin, and an increase in lipid lowering effects. Unlike SLCO1B1 and CYP genes, there is no star(*) allele nomenclature to represent ABCG2 variants at this time.
The SmPC for rosuvastatin recommends that for patients known to have homozygous loss-of-function variants for either gene (SLCO1B1 c.521 C/C genotype, or ABCG2 c.421 A/A genotype), half of the usual dose should be used, with a maximum once daily dose of 20mg.
The main benefit of pharmacogenetic testing for rosuvastatin 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 rosuvastatin.
Therapeutic recommendations
SLCO1B1
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 >20mg daily.
- Consider additional risk factors for SRM when determining starting dose (see Further Information).
- 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 half of the usual starting dose, and titrate to a maximum once daily dose of 20 mg. If >20mg daily is required, consider combination therapy with a non-statin cholesterol lowering agent.
- Consider additional risk factors for SRM when determining starting dose (see Further Information).
- 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.
ABCG2
ABCG2 status unknown
- Initiate and titrate according to disease-specific guidelines.
ABCG2 normal function
Some examples of ABCG2 genotypes include: c.421C/C
- Initiate and titrate according to disease-specific guidelines.
ABCG2 decreased function
Some examples of ABCG2 genotypes include: c.421C/A
- Increased plasma levels compared to individuals with ABCG2 normal function.
- Initiate and titrate according to disease-specific guidelines.
- Consider additional risk factors for SRM when determining starting dose (see Further Information).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
ABCG2 poor function
Some examples of ABCG2 genotypes include: c.421A/A
- Increased plasma levels compared to individuals with ABCG2 normal or decreased function.
- Initiate with half of the usual starting dose, and titrate to a maximum once daily dose of 20 mg. If >20mg daily is required, consider combination therapy with a non-statin cholesterol lowering agent.
- Consider additional risk factors for SRM when determining starting dose (see Further Information).
- Monitor for adverse effects and advise patient on action to take if they experience muscle toxicity symptoms.
SLCO1B1 and ABCG2 combined therapeutic recommendations
- Evidence for dose adjustments based on combined genotype or phenotype information is limited.
- Combinations of SLCO1B1 and ABCG2 variants and phenotypes are likely to have additive effects on the pharmacokinetics of rosuvastatin.
- Where the phenotype of one gene recommends a greater dose reduction than the other, follow the greater dose reduction of the two recommendations.
- Where a patient has both SLCO1B1 and ABCG2 decreased function, initiate with half of the usual starting dose, and keep the dose as low as possible. If >20mg is required, consider combination therapy with a non-statin cholesterol lowering agent or consider an alternative statin.
- Where a patient has both SLCO1B1 and ABCG2 poor function, initiate with half the usual starting dose, and keep the dose as low as possible. If >10mg is required, consider combination therapy with a non-statin cholesterol lowering agent or consider an alternative statin.
Further information
Drug interactions
The effects of drug-drug interactions with rosuvastatin may be more pronounced in people with reduced SLCO1B1 or ABCG2 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 substances that inhibit certain transporter pathways (e.g. SLCO1B1, BCRP) may increase rosuvastatin plasma concentrations and may lead to an increased risk of myopathy or rhabdomyolysis. Consult the SmPC of rosuvastatin and of all concomitantly used drugs to obtain further information about their potential interactions with rosuvastatin.
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. The SmPC for rosuvastatin recommends a usual starting dose of 5mg in patients with predisposing factors to myopathy. In patients with significant additional risk factors for SRM and loss of function variants in either SLCO1B1 or ABCG2, it is recommended to keep the dose as low as possible (e.g. by adding a non-statin cholesterol lowering agent) or to consider an alternative statin.
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.
Alternative statins in individuals with reduced SLCO1B1 or ABCG2 function
Atorvastatin is influenced to a similar extent by SLCO1B1 variation. Fluvastatin and pravastatin are influenced to a lesser extent by SLCO1B1 variation. Atorvastatin pharmacokinetics may also be affected by variations in the ABCG2 gene, however the clinical relevance is less established. 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.
AstraZeneca (2026) Crestor 40mg Tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/7554/smpc (Accessed online: 2/3/2026).
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.
