The Authority of Gene Modifiers in β-Thalassemia Major and Its Relationship to the Pathophysiology of the Disease

Eman Nasr Eldin, Sally A. Sayed, Asmaa M. Ismail, Hebat Alla Abdellatif , Naglaa K. Idriss, Alaa S. Abde-Elkader


β-Thalassemia, an inherited red blood cell disorder, presents a significant health problem worldwide and is caused by defects in the β-globin gene, resulting in the reduction or absence of β-globin chain synthesis. That leads to blood transfusion dependency with its terrible complications. Polymorphisms at position -158 of XmnI-HBG2 on chromosome 11 and BCL11A site on chromosome 2p16 might be linked with elevated hemoglobin F (HbF) appearance, which may, in turn, improve β-thalassemia sternness. This study aims to walk around the amending effects of XmnI and BCL11A loci on HbF levels in Egyptian β-thalassemia patients. Material and Methods. A prospective case-control study of 70 multi-transfused β-thalassemia major patients and 22 controls was performed in the Paediatric hematology unit of Assiut university hospital from June 2019 till April 2021. PCR-RFLP was used to detect single nucleotide polymorphisms at XmnI and BCL11A site loci. Results. XmnI Polymorphism was detected in 9 of 70 patients and associated with higher mean HbF levels (53.48%) than patients without polymorphism (mean Hb level was 42.23%)(P-Value=0.035). The frequency of CT heterozygous genotype was 8 (11.4%), TT homozygous genotype was (1.4%), while the wild genotype CC was detected in 61 (87.1%) of the cases. While BCL11A Polymorphism detected in 21 of 70 patients did not affect either Hb or HbF levels (P-Value =0.26). The TT genotype frequency was 49 (70%), and TC heterozygous genotype was detected in 21 (30 %) of patients. The CC genotype was absent. Conclusion: XmnI -158Gγ polymorphism, but not BCL11A polymorphism, has a modifying effect on both Hb and HbF levels in Egyptian β-thalassaemia major patients. Our research goal is to investigate the frequency of XmnI and BCL11A polymorphism in thalassemia major and investigate the HbF level difference according to the XmnI and BCL11A polymorphism of phenotype group in thalassemia major.


Keywords: β-Thalassemia major, XmnI polymorphism, BCL11A polymorphism.


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