Selenoprotein synthesis and side-effects of statins

Lancet. 2004 Mar 13;363(9412):892-4. doi: 10.1016/S0140-6736(04)15739-5.

Abstract

Statins are possibly the most effective drugs for the prevention and treatment of hypercholesterolaemia and coronary heart disease. They are generally well tolerated, however, they do cause some unusual side-effects with potentially severe consequences, most prominently myopathy or rhabdomyolysis and polyneuropathy. We noted that the pattern of side-effects associated with statins resembles the pathology of selenium deficiency, and postulated that the mechanism lay in a well established, but often overlooked, biochemical pathway--the isopentenylation of selenocysteine-tRNA([Ser]Sec). A negative effect of statins on selenoprotein synthesis does seem to explain many of the enigmatic effects and side-effects of statins, in particular, statin-induced myopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Coronary Disease / drug therapy
  • Coronary Disease / prevention & control
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / prevention & control
  • Models, Biological
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / metabolism
  • Polyneuropathies / chemically induced
  • Polyneuropathies / metabolism
  • Protein Biosynthesis*
  • Proteins / metabolism
  • Rhabdomyolysis / chemically induced
  • Rhabdomyolysis / metabolism
  • Selenium / deficiency
  • Selenium / metabolism
  • Selenoproteins

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Proteins
  • Selenoproteins
  • Selenium