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. The effect is strongest for simvastatin, large for pitavastatin, moderate for atorvastatin, and smallest for rosuvastatin, pravastatin, and fluvastatin — which is why those are common alternatives for people at higher genetic risk.
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 genotype into a transporter phenotype — normal, decreased, or poor function — and ties each to statin-specific guidance.
A rare case where one SNP changes a prescription.
SLCO1B1 has a peer-reviewed CPIC guideline (first published 2012, updated 2014 and 2022) for statin-associated muscle symptoms. The recommendations are practical:
- Simvastatin: CPIC advises against simvastatin 40 mg or 80 mg for decreased- and poor-function patients, and suggests a lower dose or an alternative statin. The FDA also restricts simvastatin 80 mg generally because of myopathy risk.
- Other statins: the 2022 update extends guidance to atorvastatin, pitavastatin, rosuvastatin, pravastatin, fluvastatin and lovastatin — generally favouring rosuvastatin/pravastatin/fluvastatin (less OATP1B1-dependent) for higher-risk genotypes.
- 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 tells you whether the standard dose is likely to make your muscles ache. 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; 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 clinical signal is one well-genotyped SNP:
- rs4149056 — almost always genotyped on consumer arrays. T/T is normal function; one C allele is decreased function; C/C is poor function. That single readout maps cleanly onto CPIC's statin guidance.
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 statin muscle symptoms, your rs4149056 result is exactly the kind of context a pharmacogenomic report is designed to surface.