STATINS

Statins is a drug class that is used to reduce the level of cholesterol in the blood by decreasing the production of cholesterol in the liver. Statins block the enzyme that is responsible for producing cholesterol in the liver. Cholesterol is needed for the normal function of every cell in the body, but at the same time it contributes to the development of atherosclerosis. Atherosclerosis is a condition which results in the formation of cholesterol-containing plaques in the arteries. Formation of these plaques can result in chest pain, heart attack, stroke. In the USA, more than 40% of people ages 60 and older are taking statins to reduce their risk of heart attack.

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According to Estonian Medicine Agency Rosuvastatin was the 4th top most used medicine in 2016.

Half of the people who are prescribed statins quit taking them because of muscle pain (myopathy) which is a serious side effect of statins. Statin-induced myopathy is quite rare but very serious, affecting ca one in 1000 people who are taking statins. If one of your relatives have had statin-induced myopathy or if you develop muscle pain, weakness during statin treatment, then it is useful to test your genotype, so the doctor can change your dose, statin type or take you off the drug. Creatine kinase (CK) levels should be monitored routinely in patients with statin treatment: CK level rises in response to muscle damage.

Statins metabolism is associated with SLCO1B1 gene and rs4149056/rs4363657markers. Statin-induced myopathy is caused by SLCO1B1*5 allele (C), which interferes with the transport of statins and causes higher systemic statin concentrations.

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C : C
Higher myopathy risk

C : T
Lower myopathy risk

T : T
Normal myopathy risk

C:C genotype indicates higher myopathy risk. About 2% of people have two copies of the risk allele (C), resulting in 17 times higher risk for developing statin-induced severe myopathy. This genotype is associated with reduced breakdown of some drugs. Statin users with C:C genotype are recommended to take lower doses of statins, 20 mg/daily, or change to some other type of statin (e.g. pravastatin, rosuvastatin). Routine surveillance of creatine kinase levels is advised.

C:T genotype indicates lower myopathy risk. These patients have decreased metabolism of statins. About 23% of people have one copy of the risk allele (C), resulting in four to five times bigger risk for myopathy.

T:T genotype indicates no risk for myopathy. About 75% of people who are taking statins have two normal alleles of SLCO1B1 gene, resulting in normal metabolism of statins and no risk for severe myopathy. Standard doses of statins can be used for this genotype.

One study made among Estonian gene donors and e-prescription users states that people with the  C:C or C:T genotype have 41% greater risk of dropping out from the statin treatment plan than people with the genotype T:T.

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SIDE EFFECTS

The most severe and rare side effects of statins are liver failure and death/injury of muscle tissue. The most common side effects of statins are:

  • Headache
  • Weakness
  • Muscle pain, cramps
  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation
  • Rash

EXAMPLES OF STATINS

  • Simvastatin (Zocor)
  • Atorvastatin (Lipitor, Atorvastatin Actavis)
  • Fluvastatin (Lescol)
  • Lovastatin (Mevacor, Altoprev)
  • Pravastatin (Pravachol)
  • Pitavastatin (Livalo)
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References
  • The SEARCH Collaborative Group. SLCO1B1 Variants and Statin-Induced Myopathy — A Genomewide Study. N Engl J Med. (2008). 359:789-99.
  • Voora D., Shah SH., Spasojevic I., Ali S. et al. The SLCO1B1*5 Genetic Variant is Associated with Statin-Induced Side Effects. J Am Coll Cardiol. (2009). 54(17): 1609–1616.
  • Pasanen MK., Backman JT., Neuvonen PJ. and Niemi M. Frequencies of single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in a Finnish population. Eur J Clin Pharmacol. (2006). 62: 409–415.
  • Tomaszewski M, Stępień KM, Tomaszewska J, Czuczwar SJ. Statin-induced myopathies. Pharmacol Rep. (2011). 63(4):859-66
  • https://www.medicinenet.com/statins/article.htm#are_there_differences_among_statins
  • https://www.health.harvard.edu/blog/muscle-problems-caused-by-statins-can-a-genetic-test-reveal-your-risk-201603039247
  • https://www.healthline.com/health/what-is-statin-induced-myopathy-or-muscle-pain#symptoms
  • https://www.bostonheartdiagnostics.com/science_portfolio_statin.php
  • https://ravimiamet.ee/sites/default/files/ravimiamet_aastaraamat_a5_100lkkaaned_k3_final.pdf
  • https://dspace.ut.ee/bitstream/handle/10062/52395/haviko_enelin_bsc_2016.pdf?sequence=1&isAllowed=y
Disclaimer

The information provided in this article is based on published SNP (single nucleotide polymorphism) data and is for educational purposes only. Most published studies about genetic variants in the DNA explain only a small part of the heritability of a trait or disease risk, and often do not take into account how different variants may interact with each other. In addition, many published studies do not account for medical history or environmental, dietary, microbial, or lifestyle factors, which may alter true risk for any trait or disease.

The relevance of each article may vary based on ethnicity. Nothing in the genetic article should be used for medical self-diagnosis or self-treatment. The information provided should not be considered complete, nor should it be relied on to suggest diagnosis or treatment of a particular individual. You should always get the advice of your doctor or other appropriate health care professional if you have any questions about diagnosis, treatment, prevention, mitigation, or cure of any medical condition, phenotype, condition, impairment, or the status of your health.

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