Gene polymorphisms predicting response to hydroxyurea treatment in Bahraini patients with sickle cell disease.

IF 2.1 4区医学 Q2 HEMATOLOGY

Expert Review of Hematology Pub Date : 2025-08-13 DOI:10.1080/17474086.2025.2546575

Fatimah S Alshaikh, Abdelhalim Deifalla, Reginald P Sequeira, Alexander Woodman

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引用次数: 0

Abstract

Background: This study investigated the association between response to hydroxyurea (HU) treatment and fetal hemoglobin (HbF), and the prevalence of mutations that regulate HbF synthesis, drug transport and biotransformation in sickle cell disease (SCD) patients.

Research design and methods: Study included n = 390 Bahrainis with a history of sickle cell crises. Responders (n = 127; 68%) were patients achieving HbF ≥ 15% along with other improvements. Non-responders (n = 60; 32%) failed to achieve this threshold despite maximum tolerated dose treatment.

Results: Hydroxyurea treated patients had decreased frequency of painful crises and hospitalizations, increased Hb and HbF and decreased sickle cell hemoglobin (HbS), and white blood cells (WBCs). The minor allele frequency of ARG2 (rs10483801), HBS1L-MYB (rs4895441), CYP2C19 (rs4986893) CYP2C19 (rs4244285), and OATP1B3 (rs3711358) gene was significantly higher in non-responders compared to responders. A negative correlation was found between the number of pain crises and hospitalizations per year and HbF%. No significant correlation was reported between the dosage and the number of hospitalizations per year. No significant correlation was found between the duration of treatment and HbF%.

Conclusions: Findings highlight the importance of a personalized treatment approach to maximize the benefits and minimize the side effects of HU, thereby improving clinical outcomes.

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巴林镰状细胞病患者对羟基脲治疗反应的基因多态性预测

背景：本研究探讨了镰状细胞病（SCD）患者对羟基脲（HU）治疗的反应与胎儿血红蛋白（HbF）之间的关系，以及调节HbF合成、药物转运和生物转化的突变的发生率。研究设计和方法：研究纳入n = 390名巴林人，有镰状细胞危象史。应答者(n = 127；68%)是HbF达到≥15%并有其他改善的患者。无应答者(n = 60；32%)未能达到这一阈值，尽管最大耐受剂量治疗。结果：羟基脲治疗患者疼痛危重和住院次数减少，Hb和HbF升高，镰状细胞血红蛋白（HbS）和白细胞（wbc）降低。ARG2 （rs10483801）、HBS1L-MYB （rs4895441）、CYP2C19 （rs4986893）、CYP2C19 （rs4244285）和OATP1B3 （rs3711358）基因的次要等位基因频率在无应答者中显著高于应答者。疼痛危机和每年住院次数与HbF%呈负相关。剂量与每年住院次数之间无显著相关性。治疗时间与HbF%之间无显著相关性。结论：研究结果强调了个性化治疗方法的重要性，以最大限度地提高胡的益处和减少副作用，从而改善临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.