| Impact of Xmn1 polymorphism on hydroxyurea therapy in children with HbE-βnon-transfusion dependent thalassemia: a cohort study |
Saheli Roy1 
, Paramita Bhattacharya2
, Atanu Kumar Dutta3
, Mrinal Kanti Das4
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1Hinduja Hospital Mumbai, Pediatrics IPGME&R, Kolkata, West Bengal, Mumbai, India
2Genetic Services Unit, Biotechnology Research Innovation Council-National Institute of Biomedical Genomics, PG Polyclinic Building, Kolkata, West Bengal, Kolkata, India
3Department of Biochemistry, AIIMS, Kalyani, West Bengal, Kalyani, India
4Department of Pediatrics, IPGME&R, Kolkata, West Bengal, Kolkata, India |
Correspondence:
Saheli Roy, Email: saheliroydr059@gmail.com
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Received: 27 August 2024 • Revised: 17 December 2024 • Accepted: 20 December 2024 |
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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 six 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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| Key Words:
HbE-B thalassemia, Fetal hemoglobin (HbF) inducers, Hydroxyurea, Genetic polymorphism, Xmn1 polymorphism |
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