{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T23:24:25Z","timestamp":1766705065980,"version":"3.48.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010724","name":"Health Systems Research Institute","doi-asserted-by":"publisher","award":["HSRI 64\u2010137"],"award-info":[{"award-number":["HSRI 64\u2010137"]}],"id":[{"id":"10.13039\/501100010724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A670732"],"award-info":[{"award-number":["N42A670732"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Deferasirox is a widely used oral iron chelator in patients with transfusion\u2010dependent thalassemia, but considerable variability in treatment response remains a clinical challenge. This study applied whole\u2010genome sequencing to investigate genetic predictors of deferasirox response in 88 Thai patients. This approach enabled comprehensive detection of both known and novel variants across eight key genes involved in deferasirox metabolism and transport. Two novel intronic variants in\n                    <jats:italic>ABCC2<\/jats:italic>\n                    emerged as strong and clinically relevant predictors of treatment response. The homozygous TG deletion variant rs3047477 in\n                    <jats:italic>ABCC2<\/jats:italic>\n                    (MAF 31.8%) was significantly associated with greater reductions in liver iron concentrations and increased iron excretion, whereas the rare variant rs188034361 was linked to poorer outcomes. Haplotype analysis identified a 69\u2010kilobase linkage block comprising 12 tightly linked variants, grouped into distinct clusters. Clusters 3.4 and 4.4 were associated with greater reductions in serum ferritin, whereas clusters 2.2, 2.3, and 4.5 predicted suboptimal response. Two variants in\n                    <jats:italic>UGT1A3<\/jats:italic>\n                    were found to have novel associations with deferasirox response. Specifically, the rs33979061 variant (MAF 6.8%) was associated with poorer treatment outcomes, whereas the rs540607993 variant (MAF 1.1%) predicted enhanced ferritin reduction. Previously reported associations involving\n                    <jats:italic>UGT1A1<\/jats:italic>\n                    (*\n                    <jats:italic>28<\/jats:italic>\n                    , *\n                    <jats:italic>6<\/jats:italic>\n                    ) and\n                    <jats:italic>UGT1A3<\/jats:italic>\n                    (rs3806596) were also confirmed. Clinical factors, including baseline iron overload, transfusion intensity, body mass index, and age, also contributed to treatment variability. These findings support the implementation of pharmacogenetic profiling to guide personalized chelation strategies in patients with transfusion\u2010dependent thalassemia.\n                  <\/jats:p>","DOI":"10.1111\/cts.70441","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:28:53Z","timestamp":1766132933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacogenomic and Clinical Predictors of Deferasirox Response in Transfusion\u2010Dependent Thalassemia Identified Using Whole\u2010Genome Sequencing"],"prefix":"10.1111","volume":"18","author":[{"given":"Kittika","family":"Yampayon","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-2646","authenticated-orcid":false,"given":"Watchara","family":"Sakares","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krittin","family":"Pitinanon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanin","family":"Limwongse","sequence":"additional","affiliation":[{"name":"Siriraj Thalassemia Center, Faculty of Medicine Siriraj Hospital Mahidol University  Bangkok Thailand"},{"name":"Siriraj Genomics, Faculty of Medicine Siriraj Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somdet","family":"Srichairatanakool","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pimpisid","family":"Koonyosying","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chonlaphat","family":"Sukasem","sequence":"additional","affiliation":[{"name":"Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital Mahidol University  Bangkok Thailand"},{"name":"Laboratory for Pharmacogenomics Ramathibodi Hospital, Somdech Phra Debaratana Medical Center SDMC  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwankom","family":"Triparn","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology National Science and Technology Development Agency  Pathum Thani Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jittima","family":"Piriyapongsa","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology National Science and Technology Development Agency  Pathum Thani Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supachai","family":"Ekwattanakit","sequence":"additional","affiliation":[{"name":"Siriraj Thalassemia Center, Faculty of Medicine Siriraj Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3162-1849","authenticated-orcid":false,"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Siriraj Genomics, Faculty of Medicine Siriraj Hospital Mahidol University  Bangkok Thailand"},{"name":"Division of Hematology\/Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-532X","authenticated-orcid":false,"given":"Varalee","family":"Yodsurang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences Chulalongkorn University  Bangkok Thailand"},{"name":"Center of Excellence in Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Chulalongkorn University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.030833"},{"volume-title":"Guidelines for the Management of Transfusion\u2010Dependent \u03b2\u2010Thalassaemia (TDT)","year":"2025","author":"Taher A. 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