title: Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.
abstract: BACKGROUND
  Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects.
  
  
  METHODS
  We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci.
  
  
  RESULTS
  Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the identification of three single-nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003-0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina.
  
  
  CONCLUSIONS
  Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle.
authors.affiliation: Department of Pediatrics, University at Buffalo, Buffalo, New York 14203, USA. isackson@buffalo.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Isackson
authors.forename: Heather M
authors.initials: HM
authors.lastname: Ochs-Balcom
authors.forename: Changxing
authors.initials: C
authors.lastname: Ma
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Wendy
authors.initials: W
authors.lastname: Peltier
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.forename: Naganand
authors.initials: N
authors.lastname: Sripathi
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wortmann
authors.forename: Zachary
authors.initials: Z
authors.lastname: Simmons
authors.forename: Jon D
authors.initials: JD
authors.lastname: Wilson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
authors.forename: Alexandru
authors.initials: A
authors.lastname: Barboi
authors.forename: Edward
authors.initials: E
authors.lastname: Fine
authors.forename: Alan
authors.initials: A
authors.lastname: Baer
authors.forename: Steven
authors.initials: S
authors.lastname: Baker
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kaufman
authors.forename: Beth
authors.initials: B
authors.lastname: Cobb
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Kilpatrick
authors.forename: Georgirene D
authors.initials: GD
authors.lastname: Vladutiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D019295:Computational Biology; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C533105:EYS protein, human; D005136:Eye Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors