Statin intolerance, genetic

EDTA blood or buccal swab

Statins are a class of drugs primarily known as HMG-CoA reductase inhibitors. Their main purpose is to regulate cholesterol metabolism in the body.

Some people may be more susceptible to statin-induced muscle pain due to their genetic predisposition (polymorphisms in the SLCO1B1 gene). SLCO1B1 is a gene that codes for the hepatic transporter OATP1B1 (organic anion transporting polypeptide 1B1). This transporter plays an important role in the uptake of various substances, including statins, into liver cells. [2]

There are varying figures on the frequency of muscle symptoms and statin therapy, ranging from 7 to 29%. [1]

The laboratory report is commented on differently depending on the genotype constellation. The laboratory findings provide you with the following information on the three possible constellations:

• Genotype TT (homozygosity): No evidence of genetically determined reduced statin elimination and no indication for a reduced dose.
• Genotype TC (heterozygosity): A heterozygous carrier shows a gene variant of SLCO1B1 that is associated with reduced transporter activity. Increased risk of muscular side effects with simvastatin/atorvastatin/pravastatin. Avoidance of the maximum dose of 80 mg recommended. If there is a lack of response to therapy at lower doses, switching to another statin is recommended (see guideline).
• Genotype CC (homozygosity): A homozygous carrier has a gene variant associated with reduced transporter activity. Significantly increased risk of muscular side effects with simvastatin/atorvastatin/pravastatin. Avoidance of doses ≥40 mg recommended. If there is a lack of response to therapy at lower doses, switching to another statin is recommended (see guideline).

The effects of SLCO1B1 polymorphism on plasma concentrations of statins are not equally strong for every active ingredient: simvastatin shows the strongest effect, followed by atorvastatin, pravastatin, rosuvastatin and finally fluvastatin, which has the least influence. [4,5]




The patient's express consent is always required for genetic testing. The relevant ‘Patient Consent Form’ can be found at the link below.



Literature
(1) Tuteja S, Rader D. SLCO1B1 and statin therapy. Getting the GIST of pharmacogenetic testing, Circ Genom Precis Med. 2018;11/9:e002320. https://doi.org/10.1161/ CIRCGEN.118.002320
(2) Pasanen M K, Neuvonen M, Neuvonen P J, Niemi M. SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenetics and genomics. 2006;16/12:873–879. https://doi.org/10.1097/01.fpc.0000230416.82349.90
(3) Search Collaborative Group. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R. SLCO1B1 variants and statin-induced myopathy- a genomewide study. The New England Journal of Medicine. 2008;359:789- 799.
(4) Niemi M, Pasanen M K, Neuvonen P J. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacological reviews. 2011;63/1:157–181. https://doi.org/10.1124/pr.110.002857
(5) Niemi M. Transporter pharmacogenetics and statin toxicity. Clinical pharmacology and therapeutics. 2010;87/1:130–133. https://doi.org/10.1038/clpt.2009.197