Rosuvastatin Pharmacogenetics - Genetic Drug Testing Gene2Rx

Drug Overview

Rosuvastatin (brand name Crestor) is a synthetic lipid-lowering agent belonging to the statin class of drugs.

It is primarily used to treat hypercholesterolemia and mixed dyslipidemia to reduce low-density lipoprotein (LDL) cholesterol and help prevent cardiovascular events.

The drug works by selectively inhibiting HMG-CoA reductase in the liver, an enzyme critical for cholesterol biosynthesis, leading to decreased cholesterol production and upregulation of LDL receptors on hepatocytes.

Relevant Genes and Their Roles

Variations in the SLCO1B1 and ABCG2 genes can influence rosuvastatin disposition. SLCO1B1 encodes a liver uptake transporter that moves rosuvastatin from the blood into liver cells. ABCG2 encodes an efflux transporter (BCRP) located in the liver and intestines that pumps rosuvastatin out of cells.

Changes in these transport proteins can alter rosuvastatin plasma levels by affecting how much drug enters liver cells or is excreted back into the bloodstream or gut. This, in turn, can impact both the drug’s effectiveness in lowering cholesterol and the risk of side effects such as muscle toxicity.

Impact of Genetics on Drug Response

Genetic differences in transporter function group patients into phenotypes—such as rapid, normal, intermediate, or poor function—that predict rosuvastatin exposure. Rapid transporter function often leads to lower blood levels, while poor function results in higher exposure. These differences influence LDL-lowering efficacy and the risk of adverse effects like myopathy.

Expected Clinical Effects of Genetic Variation

Depending on your transporter phenotype, rosuvastatin levels and muscle-related side effects can vary. Higher exposure may increase the risk of myopathy, while lower exposure can reduce efficacy. Standard dosing is generally appropriate for normal function, but adjustments or monitoring may be needed for other phenotypes.

Ultra-rapid/Rapid

Effect: Likely lower or normal plasma rosuvastatin levels due to increased transporter activity
Clinical consequence: Standard cholesterol-lowering effect with typical myopathy risk
Side effects: Muscle pain risk is low to moderate, usually mild and infrequent

Normal

Effect: Typical rosuvastatin plasma levels
Clinical consequence: Expected LDL reduction according to standard dosing
Side effects: Myopathy risk around 1–5%, generally mild

Intermediate

Effect: Moderately increased rosuvastatin exposure compared with normal function
Clinical consequence: Enhanced cholesterol reduction but higher risk of muscle side effects at high doses
Side effects: Muscle aches at higher doses; low to moderate frequency

Poor

Effect: Substantially increased plasma rosuvastatin levels
Clinical consequence: Greater LDL-lowering effect but significantly increased myopathy risk
Side effects: Muscle pain common; rare cases of severe rhabdomyolysis

Indeterminate/Not Available

Effect: Unknown
Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring

Dosing Guidelines

The following dosing guidelines are based on the CPIC guideline for statins, focusing on SLCO1B1 and ABCG2 genotype.

SLCO1B1 Dosing Guideline

Phenotype	Clinical Consequence	Guideline Recommendation
Increased Function	Your genetics suggest normal handling of rosuvastatin, so standard dosing can be used.	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.
Normal Function	Your genetics suggest normal handling of rosuvastatin, so standard dosing can be used.	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.
Decreased Function	Your genetics suggest higher rosuvastatin levels in the body, so extra care may be needed at higher doses.	Prescribe desired starting dose and adjust doses based on guidelines; be aware of increased myopathy risk at doses ≤20 mg.
Possible Decreased Function	Your genetics suggest higher rosuvastatin levels in the body, so extra care may be needed at higher doses.	Prescribe desired starting dose and adjust doses based on guidelines; be aware of increased myopathy risk at doses ≤20 mg.
Poor Function	Your genetics suggest much higher rosuvastatin levels in the body, so a lower dose is usually recommended.	Prescribe ≤20 mg as a starting dose and adjust doses based on guidelines. If higher dose is needed, consider combination therapy with non-statin agents.
Possible Poor Function	Your genetics suggest much higher rosuvastatin levels in the body, so a lower dose is usually recommended.	Prescribe ≤20 mg as a starting dose and adjust doses based on guidelines. If higher dose is needed, consider combination therapy with non-statin agents.
Indeterminate	The impact of your genotype on response to this drug is unknown.	Initiate therapy with recommended starting dose.
Not available	The impact of your genotype on response to this drug is unknown.	Initiate therapy with recommended starting dose.

ABCG2 Dosing Guideline

Phenotype	Clinical Consequence	Guideline Recommendation
Normal Function	Your genetics suggest you should respond typically to this statin with standard dosing.	Prescribe desired starting dose and adjust doses of rosuvastatin based on guidelines.
Decreased Function	Your genetics may slightly increase rosuvastatin levels, but standard dosing is usually appropriate.	Prescribe desired starting dose and adjust doses of rosuvastatin based on guidelines.
Poor Function	Your genetics suggest you may need a lower starting dose or an alternative to reduce risk of side effects and get the desired cholesterol-lowering effect.	Prescribe ≤20 mg as a starting dose and adjust doses based on guidelines. If higher dose is needed, consider an alternative statin or combination therapy.
Indeterminate	The impact of your genotype on response to this drug is unknown.	Initiate therapy with recommended starting dose.
Not available	The impact of your genotype on response to this drug is unknown.	Initiate therapy with recommended starting dose.

Alternative Treatment Options

The CPIC guideline does not specify alternative drugs for SLCO1B1 or ABCG2 variants. Clinicians may consider other statins (e.g., pravastatin or fluvastatin) or non-statin therapies (e.g., ezetimibe, PCSK9 inhibitors) based on patient tolerance and treatment goals.

Sources and References

CPIC – CPIC Guideline for Statins