ASSOCIATION OF COMMON VARIANTS IN THE HUMAN EYES SHUT ORTHOLOG (EYS) WITH STATIN-INDUCED MYOPATHY: EVIDENCE FOR ADDITIONAL FUNCTIONS OF EYS

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

来源：Muscle & Nerve, 2011, 44(4): 531-538.

DOI：10.1002/mus.22115

• agrin
• genetic association
• muscle
• myopathy
• Notch
• spinal cord
• statin

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 = 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. 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. Muscle Nerve 44: 531-538, 2011

• 出版日期2011-10