Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS

Paul J. Isackson, Heather M. Ochs-Balcom, Changxing Ma, John B. Harley, Wendy Peltier, Mark Tarnopolsky, Naganand Sripathi, Robert L. Wortmann, Zachary Simmons, Jon D. Wilson, Stephen A. Smith, Alexandru Barboi, Edward Fine, Alan Baer, Steven Baker, Kenneth Kaufman, Beth Cobb, Jeffrey R. Kilpatrick, Georgirene D. Vladutiu

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: 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 1/4 190) and statin-tolerant controls (n 1/4 130) 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 1/4 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)531-538
Number of pages8
JournalMuscle and Nerve
Volume44
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • Agrin
  • Genetic association
  • Muscle
  • Myopathy
  • Notch
  • Spinal cord
  • Statin

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS'. Together they form a unique fingerprint.

Cite this