{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:44:15Z","timestamp":1785411855390,"version":"3.56.0"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T00:00:00Z","timestamp":1552348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC0905000"],"award-info":[{"award-number":["2016YFC0905000"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2016YFC0905001"],"award-info":[{"award-number":["2016YFC0905001"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2012AA02A518"],"award-info":[{"award-number":["2012AA02A518"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2017ZX09304014"],"award-info":[{"award-number":["2017ZX09304014"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81403018"],"award-info":[{"award-number":["81403018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81522048"],"award-info":[{"award-number":["81522048"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573511"],"award-info":[{"award-number":["81573511"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81503073"],"award-info":[{"award-number":["81503073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81273595"],"award-info":[{"award-number":["81273595"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002822","name":"Central South University","doi-asserted-by":"publisher","award":["2016CX024"],"award-info":[{"award-number":["2016CX024"]}],"id":[{"id":"10.13039\/501100002822","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2015JJ3169"],"award-info":[{"award-number":["2015JJ3169"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for<jats:italic>CYP3A4<\/jats:italic>20230T&gt;C (rs2242480),<jats:italic>CYP3A4<\/jats:italic>T&gt;C (rs4646437),<jats:italic>CYP3A5<\/jats:italic>*3 6898A&gt;G (rs776746),<jats:italic>ABCB1<\/jats:italic>129T&gt;C (rs3213619);<jats:italic>ABCB1<\/jats:italic>c.1236C&gt;T (rs01128503),<jats:italic>ABCB1<\/jats:italic>c.2677G&gt;T\/A (rs2032582) and<jats:italic>ABCB1<\/jats:italic>c.3435C&gt;T (rs1045642) polymorphisms, and the effects of gene\u2010gene and gene\u2010environment interactions on the predictive accuracy of algorithm were evaluated. In wild\u2010type<jats:italic>CYP3A4<\/jats:italic>rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (<jats:italic>P<\/jats:italic>&lt; 1 \u00d7 10<jats:sup>\u22124<\/jats:sup>). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild\u2010type<jats:italic>CYP3A5<\/jats:italic>rs776746 carriers who had hypertension were higher than those without hypertension (<jats:italic>P<\/jats:italic>= 4.10 \u00d7 10<jats:sup>\u22123<\/jats:sup>). More importantly, dose\u2010predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild\u2010type<jats:italic>CYP3A4<\/jats:italic>rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and<jats:italic>CYP3A5<\/jats:italic>rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.<\/jats:p>","DOI":"10.1002\/jcph.1379","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T16:03:37Z","timestamp":1552406617000},"page":"890-899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Incorporation of Gene\u2010Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients"],"prefix":"10.1002","volume":"59","author":[{"given":"Jie","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"},{"name":"The Affiliated Zhengzhou Central Hospital of Zhengzhou University Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mou\u2010Ze","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Fang","family":"Hu","sequence":"additional","affiliation":[{"name":"Beijing Tsinghua Changgeng Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Jie","family":"Shao","sequence":"additional","affiliation":[{"name":"Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital Central South University Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital Central South University Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Wen","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Wuhan General Hospital of Guangzhou Command Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Wen","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Renal Transplantation The First Affiliated Hospital of Zhengzhou University Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Jun","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Renal Transplantation The First Affiliated Hospital of Zhengzhou University Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang\u2010Guang","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhengzhou University Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhengzhou University Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Zi","family":"Ming","sequence":"additional","affiliation":[{"name":"Research Center of Chinese Health Ministry of Transplantation Medicine Engineering and Technology, Third Affiliated Hospital Central South University Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Xiangya Hospital Central South University Hunan China"},{"name":"Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-7832","authenticated-orcid":false,"given":"Gan","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Institution of Drug Clinical Trial, Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e318198d092"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199410273311702"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200014060-00002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.10.105"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317550-000000000-00000"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/11317350-000000000-00000"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01518.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.04.006"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.109"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.199"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.113"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200212150-00002"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.17"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00168-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100216"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.11.33"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086206"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.153"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2010.00657.x"},{"issue":"2","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1515\/dmpt-2016-0036","article-title":"Influence of CYP3A4 and CYP3A5 polymorphisms on tacrolimus and sirolimus exposure in stable kidney transplant recipients","volume":"32","author":"Tamashiro EY","year":"2017","journal-title":"Drug Metabol Pers Ther"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.8.5.443"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000073901.94759.36"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2006.02.079"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2006.08.089"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200403000-00002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2005.02.073"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.210"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1083-7"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.42"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04039.x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42192"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.12.98"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12076"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1578"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05246-8"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.164"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2016.08.017"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.04.006"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100036"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2012.04694.x"},{"key":"e_1_2_10_42_1","unstructured":"LaboratoriesB.The R Project for Statistical Computing.https:\/\/www.r-project.org\/. Published 2016. Updated June 21 2016. Accessed April 10 2016."},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318200e991"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.163"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0520-8"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2797"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119100"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.392"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000151766.73249.12"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.18356"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2004.00578.x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24628"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-016-0222-x"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051551698"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051014398"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250802651984"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.26"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2010.08.012"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1379","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T18:47:17Z","timestamp":1721069237000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,12]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/jcph.1379"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1379","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,12]]},"assertion":[{"value":"2018-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}