A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance
Authors' conclusion
We provide evidence that a GRS based on four common SLCO1B1 variants provides an easily implemented genetic tool that is more reliable than the current recommended practice in estimating the risk and predicting early-onset statin intolerance.
Study context
- Population
- Statin users from Tayside, Scotland, UK
- Comparison
- High-risk SLCO1B1 gene risk score (GRS) vs low-risk GRS, compared with Val174Ala genotype alone or recommended OATP1B1 functional phenotypes
- Outcome
- Statin intolerance across three phenotypes: general statin intolerance (GSI), statin-related myopathy, statin-related suspected rhabdomyolysis
Main finding
As reported in the abstract
Statin intolerance phenotypes with high-risk GRS
High-risk GRS vs Low-risk GRSOdds ratio (95% CI)P value
General statin intolerance (GSI)
2.42(1.29–4.31)
P = 0.003Statin-related myopathy
2.51(1.28–4.53)
P = 0.004Statin-related suspected rhabdomyolysis
2.85(1.03–6.65)
P = 0.02Further findings
Meta-analysis with adjudicated statin-induced myopathy cases (PREDICTION-ADR Consortium)
- ORVal174Ala
- 1.99; 95% CI: 1.01-3.95, P = 0.048
- ORGRS
- 1.76; 95% CI: 1.16-2.69, P = 0.008
Time to onset of general statin intolerance (GSI) in those requiring high-dose statin therapy
- HRVal174Ala
- 2.49; 95% CI: 1.09-5.68, P = 0.03
- HRGRS
- 2.44; 95% CI: 1.46-4.08, P < 0.001
- High-risk GRS more consistently associated with time to onset across the three phenotypes than Val174Ala
Val174Ala alone or recommended OATP1B1 functional phenotypes
- Weaker and less reliable results
Rare SLCO1B1 variants and risk of intolerance (sequence kernel association testing)
- Rare variants in SLCO1B1 associated with risk of intolerance
- P = 0.02
Original publication
A gene risk score using missense variants in SLCO1B1 is associated with earlier onset statin intolerance. Eur Heart J Cardiovasc Pharmacother. Published 30 May 2023. doi:10.
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