Will statins give you muscle pain? What your genes can tell you.

Statins are used by tens of millions of people worldwide for lowering cholesterol levels.[ref] They nearly always top the list of most prescribed medications in the US, with Lipitor as the most prescribed drug as of July 2019. [article]

One side effect of statins is myopathy, or muscle pain and weakness.  Myopathy can be severe, leading to the breakdown of muscles and the risk of renal failure.

The risk of severe myopathy with statins is small, but myotoxicity is found in 7 to 29% of patients. Basically, this means that less severe, yet painful, muscle-related symptoms are present in quite a few patients who take statins.[ref]

Statins lower cholesterol levels by inhibiting the hydroxymethylglutaryl-coenzyme A reductase enzyme, which is part of the pathway through with the body synthesizes cholesterol. Blocking this enzyme reduces cholesterol synthesis, which leads to an increase in LDL receptor expression. More LDL receptors cause more LDL cholesterol to be removed from the bloodstream.

Before statins can act within the liver cells, though, they have to be transported into the cell via a transport protein…

The SLCO1B1 gene codes for the organic anion transporting polypeptide 1B1 (OATP1B1) protein. Genetic variants can cause this transport protein not to function as well, impairing the uptake of the statin.  This causes the statin to remain in circulation in the bloodstream, thus causing side effects such as myopathy. [ref]

The main genetic variant that impacts statin side effects is known as SLCO1B1*5 or OATP1B1 -388G>A. You can check your genetic data to see if you carry this variant.

Check your genetic data for rs4149056 (23andMe v4, v5; AncestryDNA):

  • T/T: normal
  • C/T: reduced breakdown of some drugs, a 5-fold increased risk of myopathy with statins[ref]
  • C/C: reduced breakdown of some drugs; up to a 17-fold increase in the risk of myopathy with statins[ref] [ref] [ref][ref]

Carrying this variant impacts other medications as well. If you are taking a medication that is impacted by this variant, be sure to talk with your doctor if you are having side effects from the medication. (Don’t just stop taking the drug- talk with your doc first! Read through the research studies, etc.) This list is not exhaustive, just representative of the studies from the past few years.

  • Increased risk of chemotherapy-induced amenorrhea [ref]
  • Modest changes in grazoprevir (hep-C medicine) metabolism [ref]
  • Elevated estrogen levels, and extended time of detectable estrone after aromatase inhibitor treatment (breast cancer) [ref]
  • Altered levels of letermovir (antiviral for cytomegalovirus)[ref]
  • Increased risk of liver dysfunction with tegafur-uracil[ref]
  • Decreased effectiveness of acitretin (psoriasis medication) [ref]
  • Altered response to hormone therapy in menopause.[ref]
  • Increased risk of liver dysfunction with methotrexate (lymphoma patients)[ref]
  • Decreased survival rate in high-dose methotrexate patients (ALL)[ref]
  • More information on drugs impacted by this variant: PharmGKB
  • While not as important as the drugs above, EGCG (from green tea) concentrations are affected by this variant. [ref]


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