{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:24Z","timestamp":1788412644541,"version":"build-2803163510"},"reference-count":0,"publisher":"Pakistan Journal of Medical Sciences","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pak J Med Sci"],"abstract":"<jats:p>Objectives: To assess the association of the FPN1\u20138C&gt;G polymorphism with iron overload and iron-regulatory biomarkers in transfusion-dependent \u03b2-thalassemia major patients receiving fetal hemoglobin (HbF) augmentation therapy.\nMethodology: This cross-sectional study was conducted from January 2024 to May 2025 at Fatima Hospital, Baqai Medical University, and Muhammadi Thalassemia Centre, Karachi, Pakistan. A total of 120 transfusion-dependent \u03b2-thalassemia major patients receiving hydroxyurea-based HbF augmentation therapy for at least six months were recruited through consecutive sampling. Conventional iron indices and serum hepcidin, erythroferrone (ERFE), growth differentiation factor-15 (GDF-15), and soluble transferrin receptor (sTfR) were measured. PCR-RFLP was performed for FPN1\u20138C&gt;G genotyping, with Sanger sequencing confirmation.\nResults: The FPN1\u20138C&gt;G variant was present in 39 (32.5%) patients. Iron overload was significantly associated with genotype (p=0.012). Variant carriers (CG+GG) had higher odds of iron overload than CC carriers (OR=5.67; 95% CI: 1.60\u201320.14; p=0.003), and the association remained significant after adjustment for iron-chelation regimen and duration of transfusion exposure (aOR=5.26; 95% CI: 1.43\u201319.31; p=0.012). Serum iron, ferritin, transferrin saturation, ERFE, and GDF-15 increased across CC, CG, and GG genotypes, whereas TIBC, UIBC, hepcidin, and sTfR decreased (all p&lt;0.001).\nConclusions: FPN1\u20138C&gt;G was significantly associated with greater iron burden and altered iron-regulatory biomarkers. It may represent a potential genetic marker of susceptibility to iron overload in transfusion-dependent \u03b2-thalassemia major; however, prospective validation is required.<\/jats:p>","DOI":"10.12669\/pjms.42.9.15478","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:53:30Z","timestamp":1788411210000},"page":"2567-2573","source":"Crossref","is-referenced-by-count":0,"title":["FPN1\u20138C&gt;G Polymorphism as a potential genetic modifier of iron overload in transfusion-dependent \u03b2-Thalassemia major patients receiving HbF augmentation therapy"],"prefix":"10.12669","volume":"42","author":[{"given":"Maeesa","family":"Wadood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Younus Jamal","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Iram Nazir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Muhammad Rizwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4935","published-online":{"date-parts":[[2026,9,2]]},"container-title":["Pakistan Journal of Medical Sciences"],"original-title":[],"link":[{"URL":"https:\/\/pjms.org.pk\/index.php\/pjms\/article\/download\/15478\/11661","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pjms.org.pk\/index.php\/pjms\/article\/download\/15478\/11661","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:53:30Z","timestamp":1788411210000},"score":1,"resource":{"primary":{"URL":"https:\/\/pjms.org.pk\/index.php\/pjms\/article\/view\/15478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":0,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,8,31]]}},"URL":"https:\/\/doi.org\/10.12669\/pjms.42.9.15478","relation":{},"ISSN":["1681-715X","1682-024X"],"issn-type":[{"value":"1681-715X","type":"electronic"},{"value":"1682-024X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}