Impact of Xmn1 polymorphism on hydroxyurea therapy in children with HbE-β non-transfusion dependent thalassemia: a cohort study.

IF 3.2 Q1 PEDIATRICS

Clinical and Experimental Pediatrics Pub Date : 2025-06-01 Epub Date: 2025-02-03 DOI:10.3345/cep.2024.01284

Saheli Roy, Paramita Bhattacharya, Atanu Kumar Dutta, Mrinal Kanti Das

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Abstract

Background: Fetal hemoglobin (HbF) inducers, among which hydroxyurea is the most extensively used, have shifted the paradigm toward the treatment of non-transfusion-dependent thalassemia (NTDT). Xmn1 polymorphism (rs7482144) is characterized by substitution (C>T) at -158 position of the γ-globin gene, which leads to CC, CT, or TT genotype. Recently, the role of the Xmn1 polymorphism as a modifier of hydroxyurea therapy has attracted immense research interest.

Purpose: This study aimed to estimate the prevalence of the Xmn1 polymorphism and determine its impact on the efficacy of hydroxyurea therapy in children with NTDT in Eastern India.

Methods: This observational ambispective cohort study involved the assessment of 50 patients with NTDT, of whom 28 qualified, who had been receiving hydroxyurea for less than a month. Relevant molecular analyses were performed, and data on the annual transfusion requirement (ATR), height, and HbF level before starting hydroxyurea treatment were derived from medical records. The same parameters were reassessed after 6 months of hydroxyurea therapy. Furthermore, patients were monitored for drug toxicity.

Results: All patients included in this study exhibited HbE-β-thalassemia, thus implying it to be one of the commonest NTDT genotypes in Eastern India. The prevalence rates of CC and CT were 43% and 57%, respectively, and none of the patients harbored the TT genotype. Toxicity developed in 22% of patients; however, it was not significantly associated with the Xmn1 polymorphism. Significant decrease in ATR and increase in height were observed following hydroxyurea therapy in both groups. Nevertheless, the change was more marked in CT genotype (median ATR drop: 33%, increase in median height: 3.7%, pCT=0.001) than in CC genotype (median ATR drop: 28%, increase in median height: 2.8%, pCC= 0.003).

Conclusion: The T allele of the Xmn1 polymorphism had a favorable effect on the efficacy of hydroxyurea in patients with HbE-β-NTDT.

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Xmn1多态性对HbE-β非输血依赖性地中海贫血患儿羟基脲治疗的影响：一项队列研究

背景：胎儿血红蛋白（HbF）诱导剂，其中羟基脲是使用最广泛的，已经将治疗模式转向非输血依赖型地中海贫血（NTDT）。Xmn1多态性（rs7482144）的特征是γ-珠蛋白基因-158位置的替换（C>T），导致CC、CT或TT基因型。最近，xm1多态性作为羟基脲治疗修饰剂的作用引起了广泛的研究兴趣。目的：本研究旨在估计Xmn1多态性的患病率，并确定其对羟基脲治疗印度东部NTDT患儿疗效的影响。方法：这项观察性双视角队列研究对50例NTDT患者进行了评估，其中28例合格，接受羟基脲治疗不到一个月。进行了相关的分子分析，并从医疗记录中获得了开始羟基脲治疗前的年输血需求（ATR）、身高和HbF水平的数据。羟基脲治疗6个月后重新评估相同的参数。此外，还监测了患者的药物毒性。结果：本研究中所有患者均表现出HbE-β-地中海贫血，这意味着它是印度东部最常见的NTDT基因型之一。CC和CT患病率分别为43%和57%，无TT基因型。22%的患者出现毒性；然而，它与Xmn1多态性不显著相关。两组患者经羟基脲治疗后ATR均明显降低，身高均明显增高。然而，CT基因型（ATR中位数下降33%，身高中位数增加3.7%,pCT = 0.001）比CC基因型（ATR中位数下降28%，身高中位数增加2.8%,pCC = 0.003）的变化更为明显。结论：Xmn1多态性的T等位基因对HbE-β-NTDT患者羟脲的疗效有有利影响。

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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