Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on β-thalassemia and hemoglobin E/β-thalassemia patients in Indonesia

Objective/backgroundThalassemia is a monogenic hematologic disease that has the highest prevalence globally. In addition, there is complexity of the genetic background associated with a variety of phenotypes presented among patients. Genetic heterogeneity related to fetal hemoglobin (HbF) production has been reported as an influencing phenotypic factor of β-thalassemia (β-thal). Therefore, this study aimed to find the effect of these genetic modifiers, especially in the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB), among β-thal and HbE/β-thal patients in Indonesia, according to laboratory and clinical outcomes, including HbF levels and clinical scores. This study was also designed to compare these modifying effects among β-thal and HbE/β-thal patients in Indonesia.MethodsA total of 189 patients with genotyping of β-thal and HbE/β-thal were included in this study. The erythrocytes index and Hb electrophoresis measurements were calculated using appropriate methods. The severity of β-thal and HbE/β-thal was classified based on the Mahidol score. Polymorphism of the XmnI locus, rs11886868, rs766432 (BCL11A), and rs9399137 (HBS1L-MYB) was determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and amplification refractory mutation system (ARMS) methods.ResultsThe distributions of minor allele in the XmnI locus, rs11886868, rs766432, and rs9399137 were 14%, 22%, 19% and 18% respectively. The variation allele in the XmnI locus, rs11886868, and rs766432 showed a significant value for modifying HbF and clinical score in HbE/β-thal patients, but rs9399137 did not demonstrate such features. In β-thal patients, however, no correlation was found for any single-nucleotide polymorphisms and clinical appearance.ConclusionThe XmnI locus, rs11886868, and rs766432 have a modifying effect on HbF and clinical score in HbE/β-thal patients in Indonesia, but not in β-thal patients.