Rosuvastatin: the statin where a second transporter gene joins in

The simvastatin story is about one transporter gene. Rosuvastatin is the statin that needed a second one added to the picture, and the two together are the reason this drug gets its own page rather than a footnote on the last.

Also sold as: Crestor, Ezallor.

What rosuvastatin is

Rosuvastatin is a statin, one of the cholesterol-lowering drugs taken daily to cut the long-term risk of heart attack and stroke. It is among the stronger statins and is often reached for when a lower-intensity option has not brought cholesterol down far enough. Like the rest of the class its main tolerability issue is muscle symptoms, from aching to, rarely, real muscle injury.

Why your genes come into it

A statin only works in the liver, so it has to get in and out of liver cells, and two transporter proteins do that ferrying. SLCO1B1 carries rosuvastatin into the liver; ABCG2 pumps it back out toward disposal. When either transporter has reduced function the drug clears the bloodstream more slowly, so more of it circulates in the body from the same dose, and higher circulating statin is what raises the risk of muscle symptoms. Simvastatin depends heavily on SLCO1B1 alone, which is why its page covers one gene. Rosuvastatin is a strong ABCG2 substrate as well, so a full read needs both genes, and CPIC responds by capping the starting dose where either transporter is impaired.

What published guidance says

Two tables follow, one for SLCO1B1 and one for ABCG2, and they are meant to be read together: reduced function in either transporter points the same way, and when SLCO1B1 cannot be assigned the guidance leans on the ABCG2 result instead. These rows restate CPIC's published guidance for education. They are not a dose. A statin is usually being taken to lower a real cardiovascular risk, and the dose that balances that risk against muscle symptoms is the prescriber's to set.

ABCG2

If your ABCG2 result is	What that means	Published CPIC guidance
Decreased Function	Increased rosuvastatin exposure as compared to normal function; unknown risk for myopathy; increased lipid lowering effects CPIC's combined ABCG2+SLCO1B1 guidance, shown assuming SLCO1B1 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Normal Function	Typical myopathy risk and rosuvastatin exposure CPIC's combined ABCG2+SLCO1B1 guidance, shown assuming SLCO1B1 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Poor Function	Increased rosuvastatin exposure compared to normal and decreased function; unknown myopathy risk; increased lipid-lowering effects CPIC's combined ABCG2+SLCO1B1 guidance, shown assuming SLCO1B1 is typical.	Per CPIC (A): "Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose >20mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391)."

SLCO1B1

If your SLCO1B1 result is	What that means	Published CPIC guidance
Decreased Function	Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg. CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg."
Increased Function	Typical myopathy risk and statin exposure CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Indeterminate	CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Based on ABCG2 status, prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. SLCO1B1 phenotype could not be assigned based on genotyping."
Normal Function	Typical myopathy risk and statin exposure CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines."
Poor Function	Increased rosuvastatin exposure as compared to normal function and decreased function; Typical myopathy risk with doses ≤20 mg. CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Prescribe ≤20mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. If dose > 20mg needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391)."
Possible Decreased Function	Increased rosuvastatin exposure as compared to normal function; Typical myopathy risk with doses ≤20 mg. CPIC's combined SLCO1B1+ABCG2 guidance, shown assuming ABCG2 is typical.	Per CPIC (A): "Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20mg."

Can your DNA file answer this?

The two genes are not equally readable from consumer data, which is the honest thing to know before relying on a chip. SLCO1B1 is answerable from a plain 23andMe or AncestryDNA export, because its decreased-function *5 allele is tagged by a single position, rs4149056, that consumer arrays commonly carry. ABCG2 is not on the standard chip report and is read from aligned reads in a BAM or CRAM file as part of the Deep Read panel. So a consumer file gives you one of the two transporter answers for rosuvastatin, which is genuinely useful but is half of what the drug depends on. Where a position is absent or the reads do not resolve a genotype, the result is reported as Indeterminate rather than assumed to be reference.

A genotyping chip reads only a few hundred thousand pre-selected positions, about 0.02% of your genome, chosen for common variation. It does not sequence the rest, so it cannot find the rare or novel pathogenic variants the clinical and carrier modules look for: a “no finding” from chip data means “this chip never looked”, far more so than with whole-genome sequencing. Chip data suits common-variant traits, pharmacogenomic tag SNPs, and haplogroup ancestry, not clinical or carrier screening.

See how Aimosti reports it

Common questions

I get muscle aches on rosuvastatin. Do my genes explain it?

Reduced function in SLCO1B1 or ABCG2 raises circulating statin from a given dose, and higher exposure is associated with more muscle symptoms, so it is a plausible contributor. It is not the only one: muscle symptoms on statins are common, often unrelated to genotype, and sometimes not caused by the statin at all. A result is a reason to discuss dose or drug choice with a prescriber, not a diagnosis of the ache.

Why does rosuvastatin get its own page when simvastatin already has one?

Because the genes differ. Simvastatin is graded mainly on SLCO1B1, so one table covers it. Rosuvastatin is a strong substrate for ABCG2 as well, and CPIC publishes separate guidance for each transporter, so an honest rosuvastatin page has to show both rather than borrow the simvastatin one.

If I carry a reduced-function transporter, do I have to stop the drug?

Not as a rule. The published guidance caps the starting dose rather than removing the drug, and above that cap it suggests weighing a different statin or adding a non-statin cholesterol treatment. Which route fits depends on how much cholesterol lowering you need, which is a prescribing judgement rather than a table lookup.

Can my 23andMe file answer this?

Partly. It can usually give the SLCO1B1 answer, since the key variant is a single position arrays carry. It cannot give the ABCG2 answer, which needs aligned reads and belongs to the Deep Read panel. Aimosti reads whichever the file supports and returns Indeterminate for the rest rather than guessing.