{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:19:09Z","timestamp":1784672349844,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["668353"],"award-info":[{"award-number":["668353"]}],"id":[{"id":"10.13039\/100010661","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":[[2021,9]]},"abstract":"<jats:p>Escitalopram is one of the most commonly used antidepressant drugs but exhibits a substantial interindividual variation in clinical response. A key factor underlying response differences is the polymorphic nature of the <jats:italic>CYP2C19<\/jats:italic> gene encoding the major enzyme responsible for escitalopram metabolism. Although pre\u2010emptive <jats:italic>CYP2C19<\/jats:italic> genotyping may improve escitalopram treatment outcome by dose individualization, much of the interindividual variability cannot be assigned to the currently known <jats:italic>CYP2C19<\/jats:italic> gene variants. The aim of the present study was to search for novel <jats:italic>CYP2C\u2010<\/jats:italic>haplotypes for better genetic prediction of escitalopram metabolism. First, the <jats:italic>CYP2C18\/CYP2C19<\/jats:italic> locus was sequenced from gDNA obtained from 24 patients previously genotyped as <jats:italic>CYP2C19*1\/*1<\/jats:italic> showing consistently low serum concentrations of escitalopram (&lt;\u00a025\u00a0nM\/10\u00a0mg). Three new haplotypes of the <jats:italic>CYP2C<\/jats:italic> locus (<jats:italic>CYP2C:TG<\/jats:italic>, <jats:italic>CYP2C:TA<\/jats:italic>, and <jats:italic>CYP2C:CG<\/jats:italic>) were here identified, and their functional roles were evaluated using gDNA from 875 previously genotyped escitalopram\u2010treated patients. The <jats:italic>CYP2C:CG<\/jats:italic> and <jats:italic>CYP2C:TA<\/jats:italic> haplotypes had no significant impact on escitalopram concentration. Based on the estimated effects of the novel <jats:italic>CYP2C<\/jats:italic>\u2010haplotypes on escitalopram exposure, the predicted serum concentrations of escitalopram in homozygous <jats:italic>CYP2C:TG<\/jats:italic> and <jats:italic>CYP2C19*17<\/jats:italic> carriers were 24.8% and 17.3% lower compared with the baseline (<jats:italic>CYP2C:CG and CYP2C:TA<\/jats:italic>), respectively. In conclusion, a novel <jats:italic>CYP2C<\/jats:italic>\u2010haplotype defined by rs2860840T and rs11188059G associated with ultrarapid metabolism of escitalopram was identified. Further studies should clarify the genetic basis for the enhanced escitalopram metabolism and the impact of the <jats:italic>CYP2C:TG<\/jats:italic> haplotype on the metabolism of other CYP2C19 substrates like omeprazole, voriconazole, and clopidogrel.<\/jats:p>","DOI":"10.1002\/cpt.2233","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T07:49:18Z","timestamp":1616572158000},"page":"786-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["A Novel CYP2C\u2010Haplotype Associated With Ultrarapid Metabolism of Escitalopram"],"prefix":"10.1111","volume":"110","author":[{"given":"Line Skute","family":"Br\u00e5ten","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital Oslo Norway"},{"name":"Department of Life Sciences and Health Faculty of Health Sciences OsloMet \u2013 Oslo Metropolitan University Oslo 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