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We investigated the effect of NFIB expression <jats:italic>in vitro<\/jats:italic> using 3D liver spheroids, Huh7 cells, and the influence of the <jats:italic>NFIB<\/jats:italic> polymorphism on metabolism of risperidone in patients <jats:italic>in vivo<\/jats:italic>. We found that NFIB regulates several important pharmacogenes, including <jats:italic>CYP2D6<\/jats:italic>. NFIB inhibited <jats:italic>CYP2D6<\/jats:italic> gene expression in Huh7 cells and NFIB expression in livers was predominantly nuclear and reduced at the mRNA and protein level in carriers of the <jats:italic>NFIB<\/jats:italic> rs28379954 T&gt;C allele. Based on 604 risperidone treated patients genotyped for <jats:italic>CYP2D6<\/jats:italic> and <jats:italic>NFIB<\/jats:italic>, we found that the rate of risperidone hydroxylation was elevated in <jats:italic>NFIB<\/jats:italic> rs28379954 T&gt;C carriers among CYP2D6 normal metabolizers, resulting in a similar rate of drug metabolism to what is observed in CYP2D6 ultrarapid metabolizers, with no such effect observed in CYP2D6 poor metabolizers lacking functional enzyme. The results indicate that NFIB constitutes a novel nuclear factor in the regulation of cytochrome P450 genes, and that its polymorphism is a predictor for the rate of CYP2D6 dependent drug metabolism <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cpt.2571","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T07:57:16Z","timestamp":1646639836000},"page":"1165-1174","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Polymorphic Nuclear Factor NFIB Regulates Hepatic CYP2D6 Expression and Influences Risperidone Metabolism in Psychiatric Patients"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4724-7396","authenticated-orcid":false,"given":"Hasan \u00c7a\u011f\u0131n","family":"Lenk","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Vinderen Oslo Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-5827","authenticated-orcid":false,"given":"Katharina","family":"Kl\u00f6ditz","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Section of Pharmacogenetics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-4551","authenticated-orcid":false,"given":"Inger","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Section of Pharmacogenetics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-7076","authenticated-orcid":false,"given":"Robert L\u00f8vsletten","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Vinderen Oslo Norway"},{"name":"NORMENT Institute of Clinical Medicine Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-4245","authenticated-orcid":false,"given":"Marin M.","family":"Juki\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Section of Pharmacogenetics Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Physiology Faculty of Pharmacy University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-2751","authenticated-orcid":false,"given":"Espen","family":"Molden","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Vinderen Oslo Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-9079","authenticated-orcid":false,"given":"Magnus","family":"Ingelman\u2010Sundberg","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Section of Pharmacogenetics Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500285"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2020.3643"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2246"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.650750"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.80"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30088-4"},{"key":"e_1_2_12_8_1","first-page":"eabf3637","article-title":"Toward predicting CYP2D6\u2010mediated variable drug response from CYP2D6 gene sequencing data","volume":"21","author":"Lee M","year":"2021","journal-title":"Sci. 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