Ugt1a6 Variants and Deferiprone-Induced Adrs: A Complication-Specific Analysis in Iranian Thalassemia Patients Publisher Pubmed



Najaflu M ; Neufeld EJ ; Mansourian M ; Ghanavat M ; Salehi M
Source: Pharmacogenomics Published:2025

Abstract

Aims: Deferiprone, an iron chelator, causes variable adverse drug reactions (ADRs) in β-thalassemia patients, suggesting a role for pharmacogenetic factors. To address the lack of comprehensive pharmacogenetic data, this study investigated the association between four common UGT1A6 variants–the primary enzyme metabolizing deferiprone–and the occurrence of specific ADRs, considering relevant clinical and personal characteristics. Patients & methods: A retrospective cohort of 178 Iranian β-thalassemia major patients on deferiprone was studied. ADRs–arthralgia, gastrointestinal (GI) complications, neutropenia, and liver enzyme elevations–were defined using clinical guidelines, confirmed by medical records, and supplemented by questionnaires. Four UGT1A6 polymorphisms were genotyped, and associations were evaluated using a complication-specific framework and diplotype–haplotype analyses, adjusting for ten demographic, clinical, and treatment variables. Results: Overall ADR incidence was not significantly associated with individual SNPs. Stratified analysis revealed that the AA–GC diplotype (rs2070959–rs1105879) was associated with reduced arthralgia risk (OR = 0.28, p = 0.022), whereas the GC–AC diplotype was linked to increased GI complication risk (OR = 5.48, p = 0.007) and showed a near-significant association with neutropenia. Female sex was associated only with increased GI complications (p = 0.002). Conclusions: Specific UGT1A6 diplotypes and sex are differentially associated with distinct deferiprone-related ADRs. A complication-specific pharmacogenetic approach can improve understanding of deferiprone-related ADRs. © 2026 Informa UK Limited, trading as Taylor & Francis Group.