Hemoglobin E/beta-thalassemia is a blood disorder with highly variable clinical phenotypes related to increased production of fetal hemoglobin (HbF), which can influence the degree of severity in beta-thalassemia. The aim of this study was to find out the disease modifying effects of two SNPs, rs-4671393 & rs-11886868 in BCL11A gene among HbE/beta-thalassemia patients. A total of 133 HbE/beta-thalassemia patients with mean of age 19.66 ± 10.22 years and 50 healthy controls with completely normal hematological parameters were recruited in this study and patients were classified as NTD/mild, moderate and severe, according to previously reported clinical scoring system. All the samples were subjected to Complete Blood Count analysis and Hemoglobin Electrophoresis. For SNP detection, Real-time PCR-based High Resolution Melt-Curve Analysis and Sanger Sequencing were performed. Statistical analysis including two-tailed unpaired T-test, one-way ANOVA test and Pearson Correlation were done using ‘Graphpad Prism version 7’. The allelic distribution of rs-4671393 in the BCL11A gene was 78.2% GG and 21.8% AG and for rs-11886868, there were 51.12% CC and 48.9% CT+TT. Both SNPs showed significant association with clinical severity score and induction of HbF (g/dl) (p= 0.03 and p= 0.02) in HbE/beta-thalassemia patients. In addition, HbF level was significantly higher (p<0.0001) in NTD/mildly severe group compared to other two groups having significant correlation with transfusion interval (r= 0.5) and clinical score (r= -0.45), while showed comparatively less correlation with the age of first blood transfusion (r= 0.32). Nevertheless, having both SNPs (17% minor allele for rs-4671393 and 25% minor allele for rs-11886868), no induction of HbF was found among SNP positive healthy individuals. The SNPs of BCL11A, rs-11886868 and rs-4671393 have significant effects on both HbF and clinical score in HbE/beta-thalassemia patients. However, any of the two SNPs showed no HbF inductive effect in the absence of anemic condition.
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