Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS
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 t...
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| Veröffentlicht in: | Muscle & nerve 2011-10, Vol.44 (4), p.531-538 |
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| creator | 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. |
| description | 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, 2011 |
| doi_str_mv | 10.1002/mus.22115 |
| format | Article |
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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, 2011</description><identifier>ISSN: 0148-639X</identifier><identifier>EISSN: 1097-4598</identifier><identifier>DOI: 10.1002/mus.22115</identifier><identifier>PMID: 21826682</identifier><identifier>CODEN: MUNEDE</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Aged, 80 and over ; agrin ; Biological and medical sciences ; Chromosomes, Human, Pair 6 - genetics ; Computational Biology ; Exons - genetics ; Eye and associated structures. Visual pathways and centers. Vision ; Eye Proteins - genetics ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Frequency ; genetic association ; Genome-Wide Association Study ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects ; Male ; Middle Aged ; muscle ; Muscle, Skeletal - pathology ; Muscular Diseases - chemically induced ; Muscular Diseases - genetics ; Muscular Diseases - pathology ; myopathy ; Notch ; Polymorphism, Single Nucleotide - genetics ; spinal cord ; statin ; Striated muscle. Tendons ; Vertebrates: nervous system and sense organs ; Vertebrates: osteoarticular system, musculoskeletal system ; Young Adult</subject><ispartof>Muscle & nerve, 2011-10, Vol.44 (4), p.531-538</ispartof><rights>Copyright © 2011 Wiley Periodicals, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4275-1d70a8e300462772d32d4de5241aac44232c5c82725198ed953d3a3c7d79a283</citedby><cites>FETCH-LOGICAL-c4275-1d70a8e300462772d32d4de5241aac44232c5c82725198ed953d3a3c7d79a283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmus.22115$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmus.22115$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24570837$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21826682$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isackson, Paul J.</creatorcontrib><creatorcontrib>Ochs-Balcom, Heather M.</creatorcontrib><creatorcontrib>Ma, Changxing</creatorcontrib><creatorcontrib>Harley, John B.</creatorcontrib><creatorcontrib>Peltier, Wendy</creatorcontrib><creatorcontrib>Tarnopolsky, Mark</creatorcontrib><creatorcontrib>Sripathi, Naganand</creatorcontrib><creatorcontrib>Wortmann, Robert L.</creatorcontrib><creatorcontrib>Simmons, Zachary</creatorcontrib><creatorcontrib>Wilson, Jon D.</creatorcontrib><creatorcontrib>Smith, Stephen A.</creatorcontrib><creatorcontrib>Barboi, Alexandru</creatorcontrib><creatorcontrib>Fine, Edward</creatorcontrib><creatorcontrib>Baer, Alan</creatorcontrib><creatorcontrib>Baker, Steven</creatorcontrib><creatorcontrib>Kaufman, Kenneth</creatorcontrib><creatorcontrib>Cobb, Beth</creatorcontrib><creatorcontrib>Kilpatrick, Jeffrey R.</creatorcontrib><creatorcontrib>Vladutiu, Georgirene D.</creatorcontrib><title>Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS</title><title>Muscle & nerve</title><addtitle>Muscle Nerve</addtitle><description>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, 2011</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>agrin</subject><subject>Biological and medical sciences</subject><subject>Chromosomes, Human, Pair 6 - genetics</subject><subject>Computational Biology</subject><subject>Exons - genetics</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Eye Proteins - genetics</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Frequency</subject><subject>genetic association</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</subject><subject>Male</subject><subject>Middle Aged</subject><subject>muscle</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Diseases - chemically induced</subject><subject>Muscular Diseases - genetics</subject><subject>Muscular Diseases - pathology</subject><subject>myopathy</subject><subject>Notch</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>spinal cord</subject><subject>statin</subject><subject>Striated muscle. Tendons</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><subject>Young Adult</subject><issn>0148-639X</issn><issn>1097-4598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1u1DAUhS0EokPLghdA3iDRRVr_xg67Ug2l0hSkdvhbWcZ2iCGxR7bTkmfgpZth2rJide_iO-eTDgAvMDrCCJHjYcxHhGDMH4EFRo2oGG_kY7BAmMmqps3XPfAs558IISxr8RTsESxJXUuyAH9Oco7G6-JjgLGFJg7D_F3r5HUoGfoAS-dgNw46QDe5DHM3FhhT6WIff8DXy29Xh_DGlw7mMreEygc7GmfhMMWNLt30Bi6vvXXBONjGBLW1fivTPWzHYLZv3ornngPwpNV9ds_v7j5Yv1uuT99Xq49n56cnq8owIniFrUBaOooQq4kQxFJimXWcMKy1YYxQYriRRBCOG-lsw6mlmhphRaOJpPvgcFdrUsw5uVZtkh90mhRGarunmvdUf_ec2Zc7djN-H5x9IO8HnIFXd4DORvdt0sH4_I9jXCBJxcwd77gb37vp_0Z18enqXl3tEj4X9_shodMvVQsquPry4Uzh1YX4_PayUWt6C_PBnKQ</recordid><startdate>201110</startdate><enddate>201110</enddate><creator>Isackson, Paul J.</creator><creator>Ochs-Balcom, Heather M.</creator><creator>Ma, Changxing</creator><creator>Harley, John B.</creator><creator>Peltier, Wendy</creator><creator>Tarnopolsky, Mark</creator><creator>Sripathi, Naganand</creator><creator>Wortmann, Robert L.</creator><creator>Simmons, Zachary</creator><creator>Wilson, Jon D.</creator><creator>Smith, Stephen A.</creator><creator>Barboi, Alexandru</creator><creator>Fine, Edward</creator><creator>Baer, Alan</creator><creator>Baker, Steven</creator><creator>Kaufman, Kenneth</creator><creator>Cobb, Beth</creator><creator>Kilpatrick, Jeffrey R.</creator><creator>Vladutiu, Georgirene D.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201110</creationdate><title>Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4275-1d70a8e300462772d32d4de5241aac44232c5c82725198ed953d3a3c7d79a283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>agrin</topic><topic>Biological and medical sciences</topic><topic>Chromosomes, Human, Pair 6 - genetics</topic><topic>Computational Biology</topic><topic>Exons - genetics</topic><topic>Eye and associated structures. Visual pathways and centers. Vision</topic><topic>Eye Proteins - genetics</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Frequency</topic><topic>genetic association</topic><topic>Genome-Wide Association Study</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</topic><topic>Male</topic><topic>Middle Aged</topic><topic>muscle</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Diseases - chemically induced</topic><topic>Muscular Diseases - genetics</topic><topic>Muscular Diseases - pathology</topic><topic>myopathy</topic><topic>Notch</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>spinal cord</topic><topic>statin</topic><topic>Striated muscle. Tendons</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isackson, Paul J.</creatorcontrib><creatorcontrib>Ochs-Balcom, Heather M.</creatorcontrib><creatorcontrib>Ma, Changxing</creatorcontrib><creatorcontrib>Harley, John B.</creatorcontrib><creatorcontrib>Peltier, Wendy</creatorcontrib><creatorcontrib>Tarnopolsky, Mark</creatorcontrib><creatorcontrib>Sripathi, Naganand</creatorcontrib><creatorcontrib>Wortmann, Robert L.</creatorcontrib><creatorcontrib>Simmons, Zachary</creatorcontrib><creatorcontrib>Wilson, Jon D.</creatorcontrib><creatorcontrib>Smith, Stephen A.</creatorcontrib><creatorcontrib>Barboi, Alexandru</creatorcontrib><creatorcontrib>Fine, Edward</creatorcontrib><creatorcontrib>Baer, Alan</creatorcontrib><creatorcontrib>Baker, Steven</creatorcontrib><creatorcontrib>Kaufman, Kenneth</creatorcontrib><creatorcontrib>Cobb, Beth</creatorcontrib><creatorcontrib>Kilpatrick, Jeffrey R.</creatorcontrib><creatorcontrib>Vladutiu, Georgirene D.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Muscle & nerve</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isackson, Paul J.</au><au>Ochs-Balcom, Heather M.</au><au>Ma, Changxing</au><au>Harley, John B.</au><au>Peltier, Wendy</au><au>Tarnopolsky, Mark</au><au>Sripathi, Naganand</au><au>Wortmann, Robert L.</au><au>Simmons, Zachary</au><au>Wilson, Jon D.</au><au>Smith, Stephen A.</au><au>Barboi, Alexandru</au><au>Fine, Edward</au><au>Baer, Alan</au><au>Baker, Steven</au><au>Kaufman, Kenneth</au><au>Cobb, Beth</au><au>Kilpatrick, Jeffrey R.</au><au>Vladutiu, Georgirene D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS</atitle><jtitle>Muscle & nerve</jtitle><addtitle>Muscle Nerve</addtitle><date>2011-10</date><risdate>2011</risdate><volume>44</volume><issue>4</issue><spage>531</spage><epage>538</epage><pages>531-538</pages><issn>0148-639X</issn><eissn>1097-4598</eissn><coden>MUNEDE</coden><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 = 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, 2011</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21826682</pmid><doi>10.1002/mus.22115</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over agrin Biological and medical sciences Chromosomes, Human, Pair 6 - genetics Computational Biology Exons - genetics Eye and associated structures. Visual pathways and centers. Vision Eye Proteins - genetics Female Fundamental and applied biological sciences. Psychology Gene Frequency genetic association Genome-Wide Association Study Genotype Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Male Middle Aged muscle Muscle, Skeletal - pathology Muscular Diseases - chemically induced Muscular Diseases - genetics Muscular Diseases - pathology myopathy Notch Polymorphism, Single Nucleotide - genetics spinal cord statin Striated muscle. Tendons Vertebrates: nervous system and sense organs Vertebrates: osteoarticular system, musculoskeletal system Young Adult |
| title | Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: Evidence for additional functions of EYS |
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