RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms
To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls. Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls. 12 probably pathogenic...
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| Veröffentlicht in: | Pharmacogenomics 2018-11, Vol.19 (16), p.1235-1249 |
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| creator | Isackson, Paul J Wang, Jianxin Zia, Mohammad Spurgeon, Paul Levesque, Adrian Bard, Jonathan James, Smitha Nowak, Norma Lee, Tae Keun Vladutiu, Georgirene D |
| description | To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls.
Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.
12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.
Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms. |
| doi_str_mv | 10.2217/pgs-2018-0106 |
| format | Article |
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Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.
12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.
Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.</description><identifier>ISSN: 1462-2416</identifier><identifier>EISSN: 1744-8042</identifier><identifier>DOI: 10.2217/pgs-2018-0106</identifier><identifier>PMID: 30325262</identifier><language>eng</language><publisher>England: Future Medicine Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Calcium Channels - genetics ; Calcium Channels, L-Type ; Case-Control Studies ; Congenital diseases ; Female ; Fever ; Genes ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genetic Variation - genetics ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects ; Hyperthermia ; Male ; Metabolism ; Middle Aged ; Muscular Diseases - chemically induced ; Muscular Diseases - genetics ; Musculoskeletal system ; Mutation ; Myopathy ; Next-generation sequencing ; Pain ; Patients ; Plasma ; Questionnaires ; Retrospective Studies ; Ryanodine Receptor Calcium Release Channel - genetics ; Ryanodine receptors ; Statins ; Studies</subject><ispartof>Pharmacogenomics, 2018-11, Vol.19 (16), p.1235-1249</ispartof><rights>Copyright Future Medicine Ltd Nov 2018</rights><rights>2018 Future Medicine Ltd 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-89b518a4cd356ed3937522c08f8feadb22726bfaa33b98f2fb7e2ad968d55ef23</citedby><cites>FETCH-LOGICAL-c441t-89b518a4cd356ed3937522c08f8feadb22726bfaa33b98f2fb7e2ad968d55ef23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563124/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563124/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30325262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isackson, Paul J</creatorcontrib><creatorcontrib>Wang, Jianxin</creatorcontrib><creatorcontrib>Zia, Mohammad</creatorcontrib><creatorcontrib>Spurgeon, Paul</creatorcontrib><creatorcontrib>Levesque, Adrian</creatorcontrib><creatorcontrib>Bard, Jonathan</creatorcontrib><creatorcontrib>James, Smitha</creatorcontrib><creatorcontrib>Nowak, Norma</creatorcontrib><creatorcontrib>Lee, Tae Keun</creatorcontrib><creatorcontrib>Vladutiu, Georgirene D</creatorcontrib><title>RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms</title><title>Pharmacogenomics</title><addtitle>Pharmacogenomics</addtitle><description>To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls.
Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.
12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.
Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Calcium Channels - genetics</subject><subject>Calcium Channels, L-Type</subject><subject>Case-Control Studies</subject><subject>Congenital diseases</subject><subject>Female</subject><subject>Fever</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic Variation - genetics</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</subject><subject>Hyperthermia</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Muscular Diseases - chemically induced</subject><subject>Muscular Diseases - genetics</subject><subject>Musculoskeletal system</subject><subject>Mutation</subject><subject>Myopathy</subject><subject>Next-generation sequencing</subject><subject>Pain</subject><subject>Patients</subject><subject>Plasma</subject><subject>Questionnaires</subject><subject>Retrospective Studies</subject><subject>Ryanodine Receptor Calcium Release Channel - genetics</subject><subject>Ryanodine receptors</subject><subject>Statins</subject><subject>Studies</subject><issn>1462-2416</issn><issn>1744-8042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpVkctLAzEQxoMoVqtHr7LgOZpMHpu9CKX4AlHwcfAUspukpnR36yat9L93S2vR0wwzP775mA-hM0ouAWh-NZ9EDIQqTCiRe-iI5pxjRTjs9z2XgIFTOUDHMU4JASo5OUQDRhgIkHCEXl8-XmhmGpuNR-OnEX3NJq5xKVTZ0nTBNClmwbomBR-czb5D-sxiMik02MTYVsGkflwvYjVzWVzV89TW8QQdeDOL7nRbh-j99uZtfI8fn-8exqNHXHFOE1ZFKagyvLJMSGdZwXIBUBHllXfGlgA5yNIbw1hZKA--zB0YW0hlhXAe2BBdb3Tni7J2tuptdmam512oTbfSrQn6_6YJn3rSLrUUklHgvcDFVqBrvxYuJj1tF13Te9bAQBZcgBI9hTdU1bUxds7vLlCi1xnoPgO9zkCvM-j587-2dvTv09kPfjaDdA</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Isackson, Paul J</creator><creator>Wang, Jianxin</creator><creator>Zia, Mohammad</creator><creator>Spurgeon, Paul</creator><creator>Levesque, Adrian</creator><creator>Bard, Jonathan</creator><creator>James, Smitha</creator><creator>Nowak, Norma</creator><creator>Lee, Tae Keun</creator><creator>Vladutiu, Georgirene D</creator><general>Future Medicine Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>EHMNL</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20181101</creationdate><title>RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms</title><author>Isackson, Paul J ; Wang, Jianxin ; Zia, Mohammad ; Spurgeon, Paul ; Levesque, Adrian ; Bard, Jonathan ; James, Smitha ; Nowak, Norma ; Lee, Tae Keun ; Vladutiu, Georgirene D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-89b518a4cd356ed3937522c08f8feadb22726bfaa33b98f2fb7e2ad968d55ef23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Calcium Channels - genetics</topic><topic>Calcium Channels, L-Type</topic><topic>Case-Control Studies</topic><topic>Congenital diseases</topic><topic>Female</topic><topic>Fever</topic><topic>Genes</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genetic Variation - genetics</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</topic><topic>Hyperthermia</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Muscular Diseases - chemically induced</topic><topic>Muscular Diseases - genetics</topic><topic>Musculoskeletal system</topic><topic>Mutation</topic><topic>Myopathy</topic><topic>Next-generation sequencing</topic><topic>Pain</topic><topic>Patients</topic><topic>Plasma</topic><topic>Questionnaires</topic><topic>Retrospective Studies</topic><topic>Ryanodine Receptor Calcium Release Channel - genetics</topic><topic>Ryanodine receptors</topic><topic>Statins</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isackson, Paul J</creatorcontrib><creatorcontrib>Wang, Jianxin</creatorcontrib><creatorcontrib>Zia, Mohammad</creatorcontrib><creatorcontrib>Spurgeon, Paul</creatorcontrib><creatorcontrib>Levesque, Adrian</creatorcontrib><creatorcontrib>Bard, Jonathan</creatorcontrib><creatorcontrib>James, Smitha</creatorcontrib><creatorcontrib>Nowak, Norma</creatorcontrib><creatorcontrib>Lee, Tae Keun</creatorcontrib><creatorcontrib>Vladutiu, Georgirene D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>UK & Ireland Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmacogenomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isackson, Paul J</au><au>Wang, Jianxin</au><au>Zia, Mohammad</au><au>Spurgeon, Paul</au><au>Levesque, Adrian</au><au>Bard, Jonathan</au><au>James, Smitha</au><au>Nowak, Norma</au><au>Lee, Tae Keun</au><au>Vladutiu, Georgirene D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms</atitle><jtitle>Pharmacogenomics</jtitle><addtitle>Pharmacogenomics</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>19</volume><issue>16</issue><spage>1235</spage><epage>1249</epage><pages>1235-1249</pages><issn>1462-2416</issn><eissn>1744-8042</eissn><abstract>To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls.
Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.
12 probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.
Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.</abstract><cop>England</cop><pub>Future Medicine Ltd</pub><pmid>30325262</pmid><doi>10.2217/pgs-2018-0106</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Pharmacogenomics, 2018-11, Vol.19 (16), p.1235-1249 |
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| language | eng |
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| source | MEDLINE; PubMed Central |
| subjects | Adult Aged Aged, 80 and over Calcium Channels - genetics Calcium Channels, L-Type Case-Control Studies Congenital diseases Female Fever Genes Genetic diversity Genetic Predisposition to Disease - genetics Genetic Variation - genetics Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Hyperthermia Male Metabolism Middle Aged Muscular Diseases - chemically induced Muscular Diseases - genetics Musculoskeletal system Mutation Myopathy Next-generation sequencing Pain Patients Plasma Questionnaires Retrospective Studies Ryanodine Receptor Calcium Release Channel - genetics Ryanodine receptors Statins Studies |
| title | RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms |
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