Statins

SLCO1B1 encodes OATP1B1, the liver transporter that takes statins up from the blood into liver cells. Reduced transporter function leaves more statin circulating in the body, which CPIC identifies as the likely reason for the link to statin-associated musculoskeletal symptoms. The rs4149056 (c.521T>C, p.Val174Ala) variant is the main decreased-function change and is carried within the *5 and *15 haplotypes. CPIC assigns phenotypes of increased function, normal function, decreased function, possible decreased function, poor function and indeterminate, based on the combination of alleles a person carries. A 2008 genome-wide study of patients on high-dose simvastatin found myopathy odds of 4.5 per copy of the C allele and 16.9 for two copies versus none. CPIC states that statin therapy should not be stopped or avoided because of these genotypes in someone who has an indication for a statin. No dosing information is given here.

CPIC Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Cooper-DeHoff RM et al. Clin Pharmacol Ther. 2022;111(5):1007-1021 (PMID 35152405); SEARCH Collaborative Group, N Engl J Med. 2008;359(8):789-799 (PMID 18650507).

ABCG2 encodes BCRP, an efflux transporter that moves compounds out of cells and shapes how rosuvastatin is absorbed and distributed. The common rs2231142 (c.421C>A, p.Gln141Lys) variant is associated with reduced protein expression, and rosuvastatin exposure has been reported as substantially higher in people with two copies than in those with none. CPIC assigns normal, decreased and poor function phenotypes for this gene and its recommendations for it are specific to rosuvastatin. Not currently reported by MyGeneLog.

CPIC Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Cooper-DeHoff RM et al. Clin Pharmacol Ther. 2022;111(5):1007-1021 (PMID 35152405).

CYP2C9 is a metabolising enzyme, and among the statins its genetic variation is relevant mainly to fluvastatin, where reduced-function alleles are associated with increased drug exposure. CPIC classifies CYP2C9 into normal, intermediate and poor metabolizer phenotypes using an activity score derived from the person's two alleles. The pharmacokinetics of the other statins are not meaningfully affected by CYP2C9 variation. Not currently reported by MyGeneLog.

CPIC Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Cooper-DeHoff RM et al. Clin Pharmacol Ther. 2022;111(5):1007-1021 (PMID 35152405).

Statins reliably lower cholesterol, but by how much varies from person to person. Combining genome-wide data across three statin trials — simvastatin, pravastatin and atorvastatin — in 3,932 people, the clearest signal sat near CLMN, associated with how much total cholesterol dropped on treatment (84% posterior probability, P = 1.8×10⁻⁸). A second, weaker signal in the same study — this page's other variant — sits in a region with three candidate genes (LOC646909, DUSP4, KIF13B) and was not the paper's headline finding, so it is reported here as a real but less-attributed result rather than pointing at one gene with confidence.

Barber MJ et al., PLoS One 2010 — genome-wide association of lipid-lowering response to statins across three clinical trials. PMID:20339536

Statins are prescribed to lower LDL cholesterol, but they also raise HDL cholesterol as a side effect of treatment — and that rise varies between people too. A meta-analysis of 27,720 statin-treated individuals found exactly one genome-wide significant signal for that variation, at CETP. CETP is already known for its role in baseline HDL levels; the study specifically found this treatment-response effect to be independent of that — a second, separate role for the same gene, not a restatement of it.

Postmus I et al., Open Heart 2016 — meta-analysis of genome-wide association studies of HDL cholesterol response to statins. PMID:27587472