Rosuvastatin and ABCG2

Megan Siefert, Pharm.D. Candidate; Caitlin Haack, Pharm.D. Candidate; Paige Laughlin, Pharm.D. Candidate 

About the Drug

Rosuvastatin (Crestor ®) is a medication that lowers LDL cholesterol, increases HDL cholesterol, and lowers triglycerides. Rosuvastatin helps to lower the risk of heart complications such as heart attacks and strokes.

Unlike some other statins, rosuvastatin is not a prodrug. It works by directly inhibiting HMG-CoA reductase, which prevents HMG-CoA from being converted into mevalonate, the rate-limiting component for the biosynthesis of cholesterol. Rosuvastatin also increases the uptake of cholesterol from the blood to the liver, decreasing plasma levels of cholesterol. This inhibition of HMG-CoA reductase and increased uptake lead to decreased cholesterol levels over time, and help prevent arterial blockages that cause heart attacks and strokes.

About the Gene

The gene of interest is ABCG2, which contains instructions to make the ABCG2 protein. This protein is responsible for carrying rosuvastatin throughout the body. The main variant for this gene is rs2231142.

About the Drug-Gene Interaction

Variations of the gene ABCG2 can lead to increased exposure to rosuvastatin and increased lipid-lowering effects. For patients with 2 normal function alleles or one normal and one variant allele, no changes are necessary for the dose of the drug. If a patient has 2 variant alleles, rosuvastatin doses should not exceed 20 mg. If the patient requires greater doses to achieve therapeutic goals, a different statin or a combination of rosuvastatin and another non-statin medication should be considered.

The variant allele has vastly different frequencies among different groups of people. East Asians are most likely to have this variant with 30.71% of the population having it, followed by Latinos at 22.44%. Patient ancestry should be considered when starting this medication.

Prescriber Info

The links below provide access to important articles and information relative to simvastatin. The links are to external websites and will be checked regularly for consistency.

• Rosuvastatin Prescribing Information
• Rosuvastatin Pharmacogenomic Dosing Guidelines
• Pharmacogenomics Knowledge Base: Rosuvastatin

Sources of Information

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2025. Rosuvastatin; [cited 2025 Jan 21]; [about 3 screens]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ccbaa83-d57a-421e-88a8-1cee42d4207b&audience=consumer

R.M. Cooper-DeHoff, M. Niemi, L.B. Ramsey, J.A. Luzum, E.K. Tarkiainen, R.J. Straka, L. Gong, S. Tuteja, R.A. Wilke, M. Wadelius, E.A. Larson, D.M. Roden, T.E. Klein, S..W. Yee, R.M. Krauss, R.M. Turner, L.Palaniappan, A. Gaedigk, K.M. Giacomini, K.E. Caudle and D. Voora. “The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms” Clinical Pharmacology & Therapeutics (2022) May;111(5):1007-21.

Song Y, Lim HH, Yee J, Yoon HY, Gwak HS. The Association between ABCG2 421C>A (rs2231142) Polymorphism and Rosuvastatin Pharmacokinetics: A Systematic Review and Meta-Analysis. Pharmaceutics. 2022 Feb 24;14(3):501. doi: 10.3390/pharmaceutics14030501. PMID: 35335877; PMCID: PMC8954661.