Rosuvastatin: the statin where a second transporter gene joins in

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's guidance shifts with the phenotype each one resolves to. The tables below are that guidance, restated in full, and they are the thing to read rather than any summary of them.

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?

Both transporter answers usually come from the file you already have. Each gene is graded on one position that consumer arrays commonly carry: rs4149056 is the change SLCO1B1's no-function *5 and *15 alleles share, and rs2231142 is ABCG2's decreased-function variant. Every 23andMe and AncestryDNA export we have tested carries both, so a chip report reads both, and both cards quote CPIC's row for the pair it found. Some MyHeritage, FamilyTreeDNA and Living DNA exports leave them out. From a chip or a variant file the report reads that one SLCO1B1 position; its rarer alleles come from aligned reads in the Deep Read panel. 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.