SLCO1B1
SLCO1B1 makes the liver transporter OATP1B1, which pulls statins out of your bloodstream and into the liver where they work. A common reduced-function variant lets statins build up in the blood and muscle instead — raising the risk of statin-induced muscle pain (myopathy). It is one of the clearest, most actionable pharmacogenomic results you can read from consumer DNA data.
The statin gatekeeper.
Unlike CYP enzymes, SLCO1B1 does not break down drugs — it transports them. The OATP1B1 protein sits on the surface of liver cells and ferries statins (and other organic anions, including some chemotherapy and antibiotic drugs) from the blood into the hepatocyte. For statins this is the point: they act in the liver, and efficient uptake keeps blood and muscle concentrations low.
When OATP1B1 function is reduced, statins are taken up more slowly, so systemic exposure rises and more of the drug reaches skeletal muscle — the tissue where statin toxicity shows up as aches, weakness, and, rarely, the serious muscle breakdown called rhabdomyolysis. CPIC describes increased exposure to every statin it covers when SLCO1B1 function is reduced, and gives statin-specific recommendations; for simvastatin and lovastatin it recommends an alternative statin in decreased and poor function.
SLCO1B1 affects tolerability, not whether the statin lowers cholesterol. The clinical question it answers is not "will this drug work?" but "is this dose likely to cause muscle problems for this person?"
One SNP does most of the work.
SLCO1B1 has formal star-allele nomenclature, but a single variant carries most of the clinical signal:
CPIC translates the star-allele genotype into a transporter phenotype — mainly normal, decreased, or poor function, plus rarer increased, possible decreased and indeterminate categories — and ties each to statin-specific guidance. rs4149056 tags the main decreased-function allele but is not a full star-allele call.
A rare case where one SNP changes a prescription.
SLCO1B1 has a peer-reviewed CPIC guideline (first published 2012, updated 2014; replaced in 2022 by a guideline that also covers ABCG2 and CYP2C9) for statin-associated muscle symptoms. The recommendations are practical:
- Simvastatin: CPIC 2022 recommends an alternative statin for decreased- and poor-function phenotypes; for decreased function, if simvastatin is still warranted, it limits the dose to under 20 mg/day. Separately from genotype, the FDA label sets a 40 mg/day maximum and restricts 80 mg to long-term users without muscle toxicity.
- Other statins: the 2022 update extends guidance to atorvastatin, pitavastatin, rosuvastatin, pravastatin, fluvastatin and lovastatin with genotype-specific recommendations — for poor function, starting doses of ≤20 mg atorvastatin, ≤1 mg pitavastatin, ≤20 mg rosuvastatin, ≤40 mg pravastatin or fluvastatin, and an alternative to lovastatin. It also adds ABCG2 (rosuvastatin) and CYP2C9 (fluvastatin).
- The evidence: the association comes from a genome-wide study (the SEARCH trial, NEJM 2008) and has been replicated many times — it is one of the best-established pharmacogenomic signals outside the CYP genes.
"SLCO1B1 won't tell you whether a statin lowers your cholesterol — it is linked to whether the standard dose is more likely to cause muscle symptoms, in groups defined by a validated test. For a drug taken by hundreds of millions of people, that is a useful thing to know in advance."
Primary sources: CPIC — SLCO1B1 gene page; Cooper-DeHoff et al., Clin Pharmacol Ther 2022 (CPIC statin guideline update); SEARCH Collaborative Group, N Engl J Med 2008; ZOCOR (simvastatin) prescribing information, FDA/DailyMed; PharmGKB SLCO1B1.
What consumer arrays do — and don't — tell you about SLCO1B1.
This is one of the friendliest pharmacogenes for consumer raw data, because nearly all of the known signal is at one well-genotyped SNP:
- rs4149056 — almost always genotyped on consumer arrays. Its C allele is the variant carried by *5, *15 and several rarer alleles. CPIC groups people by function phenotype from a validated test; a raw-file count at one position is not that phenotype, and it should not inform a statin choice on its own.
The honest caveats are smaller here than for CYP2D6 or CYP2C9. The main ones: rarer SLCO1B1 alleles and structural variants are not captured, the risk applies to statin tolerability (not cardiovascular benefit, which is real and important), and a raw-data genotype is information to discuss with a clinician — not a reason to stop a statin. If you have had muscle symptoms on a statin, tell your clinician; a validated pharmacogenomic test, not a raw-data file, is what can inform the choice of statin.