title: Mechanisms of statin-induced myalgia assessed by physiogenomic associations.
abstract: OBJECTIVE
  We investigated genetic variants predictive of muscular side effects in patients treated with statins. We utilized a physiogenomic approach to prototype a multi-gene panel correlated with statin-induced myalgia.
  
  
  BACKGROUND
  Statin-induced myalgia occurs in ∼10% of lipid clinic outpatients. Its clinical manifestation may depend in part upon gene variation from patient to patient.
  
  
  METHODS
  We genotyped 793 patients (377 with myalgia and 416 without) undergoing statin therapy at four U.S. outpatient clinic sites to evaluate 31 candidate genes from the literature for their association with statin-induced common myalgia.
  
  
  RESULTS
  Three previously hypothesized candidate genes were validated: COQ2 (rs4693570) encoding para-hydroxybenzoate-polyprenyltransferase, which participates in the biosynthesis of coenzyme Q10 (p<0.000041); ATP2B1 (rs17381194) which encodes a calcium transporting ATPase involved in calcium homeostasis (p<0.00079); and DMPK (rs672348) which encodes a protein kinase implicated in myotonic dystrophy (p<0.0016).
  
  
  CONCLUSIONS
  The candidate genes COQ2, ATP2B1, and DMPK, representing pathways involved in myocellular energy transfer, calcium homeostasis, and myotonic dystonia, respectively, were validated as markers for the common myalgia observed in patients receiving statin therapy. The three genes integrated into a physiogenomic predictive system could be relevant to myalgia diagnosis and prognosis in clinical practice.
authors.affiliation: Genetics Research Center, Hartford Hospital, Hartford, CT, USA. gruano@harthosp.org
authors.forename: Gualberto
authors.initials: G
authors.lastname: Ruaño
authors.forename: Andreas
authors.initials: A
authors.lastname: Windemuth
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Malloy
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: Mohan
authors.initials: M
authors.lastname: Kocherla
authors.forename: Kali
authors.initials: K
authors.lastname: Bogaard
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Gordon
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta
authors.forename: Richard L
authors.initials: RL
authors.lastname: Seip
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D006949:Hyperlipidemias / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009135:Muscular Diseases / Q000209:etiology* / Q000378:metabolism*; D010597:Pharmacogenetics
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors