title: Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy.
abstract: BACKGROUND
  Carriers of the rs4363657C and rs4149056C alleles in SLCO1B1 have increased myopathic complaints when taking simvastatin. Whether rosuvastatin has a similar effect is uncertain. This study assesses whether SLCO1B1 polymorphisms relate to clinical myalgia after rosuvastatin therapy.
  
  
  METHODS
  In the JUPITER trial, participants without prior cardiovascular disease or diabetes who had low-density lipoprotein cholesterol <130 mg/dL and C-reactive protein ≥2 mg/L were randomly allocated to rosuvastatin 20 mg or placebo and followed for the first cardiovascular disease events and adverse effects. We evaluated the effect of rs4363657 and rs4149056 in SLCO1B1, which encodes organic anion-transporting polypeptide OATP1B1, a regulator of hepatic statin uptake, on clinically reported myalgia.
  
  
  RESULTS
  Among 4,404 participants allocated to rosuvastatin, clinical myalgia occurred with a rate of 4.1 events per 100 person-years as compared with 3.7 events per 100 person-years among 4,378 participants allocated to placebo (hazard ratio [HR] 1.13, 95% CI 0.98-1.30). Among those on rosuvastatin, there were no differences in the rate of myalgia among those with the rs4363657C (HR 0.95, 95% CI 0.79-1.14 per allele) or the rs4149056C allele (HR 0.95, 95% CI 0.79-1.15 per allele) compared with those without the C allele. Similar null data were observed when the myalgia definition was broadened to include muscle weakness, stiffness, or pain. None of the 3 participants on rosuvastatin or the 3 participants on placebo with frank myopathy had the minor allele at either polymorphism.
  
  
  CONCLUSIONS
  There appears to be no increased risk of myalgia among users of rosuvastatin who carry the rs4363657C or the rs4149056C allele in SLCO1B1.
authors.affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. jdanik@partners.org
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Danik
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Jean G
authors.initials: JG
authors.lastname: MacFadyen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000483:Alleles; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004247:DNA / Q000235:genetics*; D004311:Double-Blind Method; D005464:Fluorobenzenes / Q000009:adverse effects* / Q000627:therapeutic use; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D027381:Liver-Specific Organic Anion Transporter 1; D009135:Muscular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011322:Primary Prevention; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011743:Pyrimidines; C503999:SLCO1B1 protein, human; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D004247:DNA