Roy Saheli, Bhattacharya Paramita, Dutta Atanu Kumar, Das Mrinal Kanti
P.D.Hinduja Hospital Mumbai, Pediatrics IPGME&R, Kolkata, West Bengal, Mumbai, India.
Genetic Services Unit, Biotechnology Research Innovation Council-National Institute of Biomedical Genomics, PG Polyclinic Building, Kolkata, West Bengal, Kolkata, India.
Clin Exp Pediatr. 2025 Jun;68(6):437-444. doi: 10.3345/cep.2024.01284. Epub 2025 Feb 3.
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.
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.
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.
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).
The T allele of the Xmn1 polymorphism had a favorable effect on the efficacy of hydroxyurea in patients with HbE-β-NTDT.
胎儿血红蛋白（HbF）诱导剂已改变了非输血依赖型地中海贫血（NTDT）的治疗模式，其中羟基脲是使用最广泛的。Xmn1多态性（rs7482144）的特征是γ-珠蛋白基因-158位发生替换（C>T），导致CC、CT或TT基因型。最近，Xmn1多态性作为羟基脲治疗修饰因子的作用引起了极大的研究兴趣。
本研究旨在评估印度东部NTDT儿童中Xmn1多态性的患病率，并确定其对羟基脲治疗疗效的影响。
这项观察性双向队列研究涉及对50例NTDT患者的评估，其中28例符合条件，他们接受羟基脲治疗不到一个月。进行了相关分子分析，开始羟基脲治疗前的年度输血需求量（ATR）、身高和HbF水平数据来自病历。羟基脲治疗6个月后重新评估相同参数。此外，对患者进行药物毒性监测。
本研究纳入的所有患者均表现为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的患病率分别为43%和57%，没有患者携带TT基因型。22%的患者出现毒性反应；然而，它与Xmn1多态性无显著相关性。两组患者在羟基脲治疗后均观察到ATR显著降低和身高增加。然而，CT基因型（中位ATR下降：33%，中位身高增加：3.7%，pCT = 0.001）的变化比CC基因型（中位ATR下降：28%，中位身高增加：2.8%，pCC = 0.003）更明显。
Xmn1多态性的T等位基因对HbE-β-NTDT患者的羟基脲疗效有有利影响。
