{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:08:58Z","timestamp":1792760938994,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G1000417"],"award-info":[{"award-number":["G1000417"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>Atorvastatin (ATV) is frequently prescribed and generally well \u00a0tolerated, but can lead to myotoxicity, especially at higher doses. A genome\u2010wide association study of circulating levels of ATV, 2\u2010hydroxy (2\u2010OH) ATV, ATV lactone (ATV L), and 2\u2010OH ATV L was performed in 590 patients who had been hospitalized with a non\u2010ST elevation acute coronary syndrome 1\u00a0month earlier and were on high\u2010dose ATV (80\u00a0mg or 40\u00a0mg daily). The <jats:italic>UGT1A<\/jats:italic> locus (lead single nucleotide polymorphism, rs887829) was strongly associated with both increased 2\u2010OH ATV\/ATV (<jats:italic>P<\/jats:italic>\u00a0=\u00a07.25\u00a0\u00d7\u00a010<jats:sup>\u221216<\/jats:sup>) and 2\u2010OH ATV L\/ATV L (<jats:italic>P<\/jats:italic>\u00a0=\u00a03.95\u00a0\u00d7\u00a010<jats:sup>\u221215<\/jats:sup>) metabolic ratios. Moreover, rs45446698, which tags <jats:italic>CYP3A7*1C<\/jats:italic>, was nominally associated with increased 2\u2010OH ATV\/ATV (<jats:italic>P<\/jats:italic>\u00a0=\u00a06.18\u00a0\u00d7\u00a010<jats:sup>\u22127<\/jats:sup>), and <jats:italic>SLCO1B1<\/jats:italic> rs4149056 with increased ATV (<jats:italic>P<\/jats:italic>\u00a0=\u00a02.21\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>) and 2\u2010OH ATV (<jats:italic>P<\/jats:italic>\u00a0=\u00a01.09\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>) levels. In a subset of these patients whose levels of ATV and metabolites had also been measured at 12\u00a0months after hospitalization (<jats:italic>n<\/jats:italic>\u00a0=\u00a0149), all of these associations remained, except for 2\u2010OH ATV and rs4149056 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.057). Clinically, rs4149056 was associated with increased muscular symptoms (odds ratio (OR) 3.97; 95% confidence interval (CI) 1.29\u201312.27; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.016) and ATV intolerance (OR 1.55; 95% CI 1.09\u20132.19; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014) in patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a0870) primarily discharged on high\u2010dose ATV. In summary, both novel and recognized genetic associations have been identified with circulating levels of ATV and its major metabolites. Further study is warranted to determine the clinical utility of genotyping rs4149056 in patients on high\u2010dose ATV.<\/jats:p>","DOI":"10.1002\/cpt.1820","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T06:36:05Z","timestamp":1583303765000},"page":"287-297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["A Genome\u2010wide Association Study of Circulating Levels of Atorvastatin and Its Major Metabolites"],"prefix":"10.1111","volume":"108","author":[{"given":"Richard M.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying E.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Liverpool Liverpool UK"},{"name":"Chinese Academy of Sciences Shenzhen Institutes of Advanced Technology Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Liverpool Liverpool UK"},{"name":"Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"NICE.Cardiovascular disease: risk assessment and reduction including lipid modification (Clinical guideline 181)<https:\/\/www.nice.org.uk\/guidance\/cg181> (2016). 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