Influence of single nucleotide polymorphisms in the BCL11A, HBS1L-MYB intergenic region, and HBB gene cluster on the fetal hemoglobin levels in Bangladeshi patients with β-thalassemia/hemoglobin E disease
DOI:
https://doi.org/10.14456/gag.2017.4Keywords:
β-thalassemia, HbE, fetal hemoglobin, HbF, SNPsAbstract
Thalassemia is considered as a major health burden in the Southeast Asian and Indian populations. Patients with β-thalassemia display disease heterogeneity ranging from nearly asymptomatic to severe anemia with complications. Increased levels of fetal hemoglobin (HbF) can ameliorate the clinical severity of β-thalassemia patients. The HbF production is influenced by many quantitative trait loci (QTL). Three major HbF-QTLs are the BCL11A gene, the HBS1L-MYB intergenic region (HMIR), and the β-globin gene (HBB) cluster. Therefore, this study aimed to evaluate the influence of these genetic modifiers (BCL11A, rs766432; HMIR, rs4895411; and HBB cluster, rs2071348) on the HbF levels in Bangladeshi patients with β-thalassemia/HbE disease. The cohort study comprised of 90 patients with β-thalassemia/HbE disease, HbF levels ranged from 7.9% to 59.1%, from in and around the area of Chittagong, Southeast Bangladesh. Our results showed that levels of HbF were primarily influenced by alleles of the HBB cluster (rs2071348), and to a lesser extent by rs766432 HBL11A gene and HMIP (rs4895441) loci. The SNPs rs2071348 explained 12.5% of the variation in HbF levels, while 3.6% and 3.9% of trait variation were explained by rs766432 and rs4895441, respectively. In a case-control model of low and high HbF analysis, we found genotypes AC and AA (p = 2.0×10-4), the allele C (p = 2.0×10-4) for 2071348; genotypes AG and GG (p = 0.02), the allele G (p = 0.05) for rs4895441; all had a significantly higher frequency in the high HbF group than in the low HbF group, but rs766432 did not exhibit such features. Our results suggest these three major HbF-QTLs as the influencing phenotypic factors of β-thalassemia in Bangladeshi β-thalassemia/HbE patients.
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