Single Nucleotide Polymorphisms in XMN1-HBG2, HBS1L-MYB, and BCL11A and Their Relation to High Fetal Hemoglobin Levels That Alleviate Anemia

Abstract

Anemia is a condition in which red blood cells and/or hemoglobin (Hb) concentrations are decreased below the normal range, resulting in a lack of oxygen being transported to tissues and organs. Those afflicted with this condition may feel lethargic and weak, which reduces their quality of life. The condition may be manifested in inherited blood disorders, such as thalassemia and sickle cell disease, whereas acquired disorders include aplastic anemia, chronic disease, drug toxicity, pregnancy, and nutritional deficiency. The augmentation of fetal hemoglobin (HbF) results in the reduction in clinical symptoms in beta-hemoglobinopathies. Several transcription factors as well as medications such as hydroxyurea may help red blood cells produce more HbF. HbF expression increases with the downregulation of three main quantitative trait loci, namely, the XMN1-HBG2, HBS1L-MYB, and BCL11A genes. These genes contain single nucleotide polymorphisms (SNPs) that modulate the expression of HbF differently in various populations. Allele discrimination is important in SNP genotyping and is widely applied in many assays. In conclusion, the expression of HbF with a genetic modifier is crucial in determining the severity of anemic diseases, and genetic modification of HbF expression may offer clinical benefits in diagnosis and disease management.

Population characterization of mutations for sickle cell anemia and its treatment: One step towards personalized medicine for the disease

“…Un hecho interesante es que muchos pacientes ya tenían un HF basal más alto y presentaban muchos SNPs en los genes BCL11A, HMIP (polimorfismo intergénico HbS1L-MYB) y HBG2. 31 . El gen BCL11A es un factor de transcripción que codifica una proteína de dedos de zinc y está asociado al desarrollo de varias neoplasias linfoides 32 .…”

Molecular understanding of unusual HbE-β + -thalassemia with Hb phenotype similar to HbE heterozygote: simple and rapid differentiation using HbE levels

“…Our results emphasized that the C allele was associated with the type of βmutation rather than with HbF expression in patients with HbE-β + -thalassemia. Previous studies have demonstrated that in HbE-β-thalassemia, the T allele or T/T genotype is also associated with increased HbF and milder anemia [ 6 , 41 ]. However, in our study, the T allele was identified in a relatively low proportion of patients with both low and high HbF levels ( Table 5 ).…”