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 journalArticle

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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 1 2011

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Muscular Diseases
Agrin
Chromosomes, Human, Pair 6
Genetic Loci
Genome-Wide Association Study
Genetic Predisposition to Disease
Genes
Single Nucleotide Polymorphism
Retina
Regeneration
Spinal Cord
Skeletal Muscle
Complementary DNA
Maintenance

All Science Journal Classification (ASJC) codes

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

Cite this

Isackson, P. J., Ochs-Balcom, H. M., Ma, C., Harley, J. B., Peltier, W., Tarnopolsky, M., ... Vladutiu, G. D. (2011). Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS. Muscle and Nerve, 44(4), 531-538. https://doi.org/10.1002/mus.22115
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. / Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy : Evidence for additional functions of EYS. In: Muscle and Nerve. 2011 ; Vol. 44, No. 4. pp. 531-538.
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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.",
author = "Isackson, {Paul J.} and Ochs-Balcom, {Heather M.} and Changxing Ma and Harley, {John B.} and Wendy Peltier and Mark Tarnopolsky and Naganand Sripathi and Wortmann, {Robert L.} and Zachary Simmons and Wilson, {Jon D.} and Smith, {Stephen A.} and Alexandru Barboi and Edward Fine and Alan Baer and Steven Baker and Kenneth Kaufman and Beth Cobb and Kilpatrick, {Jeffrey R.} and Vladutiu, {Georgirene D.}",
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Isackson, PJ, Ochs-Balcom, HM, Ma, C, Harley, JB, Peltier, W, Tarnopolsky, M, Sripathi, N, Wortmann, RL, Simmons, Z, Wilson, JD, Smith, SA, Barboi, A, Fine, E, Baer, A, Baker, S, Kaufman, K, Cobb, B, Kilpatrick, JR & Vladutiu, GD 2011, 'Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS', Muscle and Nerve, vol. 44, no. 4, pp. 531-538. https://doi.org/10.1002/mus.22115

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

In: Muscle and Nerve, Vol. 44, No. 4, 01.10.2011, p. 531-538.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy

T2 - Evidence for additional functions of EYS

AU - Isackson, Paul J.

AU - Ochs-Balcom, Heather M.

AU - Ma, Changxing

AU - Harley, John B.

AU - Peltier, Wendy

AU - Tarnopolsky, Mark

AU - Sripathi, Naganand

AU - Wortmann, Robert L.

AU - Simmons, Zachary

AU - Wilson, Jon D.

AU - Smith, Stephen A.

AU - Barboi, Alexandru

AU - Fine, Edward

AU - Baer, Alan

AU - Baker, Steven

AU - Kaufman, Kenneth

AU - Cobb, Beth

AU - Kilpatrick, Jeffrey R.

AU - Vladutiu, Georgirene D.

PY - 2011/10/1

Y1 - 2011/10/1

N2 - 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.

AB - 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.

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