Association of alpha hemoglobin–stabilizing protein (AHSP) gene mutation and disease severity among HbE—beta thalassemia patients
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In this study, we aimed to investigate the pattern and association of genetic mutations occurring within the alpha hemoglobin–stabilizing protein (AHSP) gene among HbE beta thalassemia patients with varying phenotypic expressions. Fifty-four diagnosed cases of HbE beta thalassemia (transfusion dependent and independent) were included in the study. Among them, 38 patients with similar genotypes (IVS 1–5, alpha gene deletion and triplication, Xmn polymorphism) were selected for further analysis. AHSP gene sequencing was done for these 38 samples to study associated mutations in AHSP gene. HbE beta thalassemia patients with similar genotypes but different phenotypic expressions were found to have mutations in the AHSP gene. There were five mutations found most prevalent among the samples analyzed for AHSP gene sequencing. Among these, two mutations were from intron 1 region of AHSP and three mutations were found in exon 3. The most prevalent mutation was found at the Oct binding site at intron 1 of AHSP. The mutations in exon 3 were more prevalent among the TDT groups. A mutation in exon 3 changing the amino acid (33rd) from serine to phenylalanine was found to be associated with only TDT group. This study documents that among the HbE beta thalassemia patients with varying severity, an exon mutation in AHSP is significantly prevalent only among the TDT group. Further understanding of the mechanism will shed light upon the impact of AHSP in modifying the disease severity in thalassemia.
KeywordsThalassemia Globin gene Transfusion Phenotype HbE beta thalassemia
Hereditary persistence of fetal hemoglobin
Alpha hemoglobin–stabilizing protein
Red blood cells
Compliance with ethical standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).
Informed consent was obtained from all patients for being included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
There is no financial relationship involved with the organization sponsored the research.
- 1.Higgs DR (1993) The thalassaemia syndromes. Q J Med 86(9):559–564Google Scholar
- 10.dos Santos CO, Zhou S, Secolin R, Wang X, Cunha AF, Higgs DR, Kwiatkowski JL, Thein SL, Gallagher PG, Costa FF, Weiss MJ (2008) Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function. Am J Hematol 83(2):103–108CrossRefGoogle Scholar
- 12.Lettre G (2012) The search for genetic modifiers of disease severity in the β-hemoglobinopathies. Cold Spring Harbor perspectives in medicine 2(10):a015032Google Scholar
- 13.Ranjbaran R, Okhovat MA, Mobarhanfard A et al (2014) Relationship between AHSP gene expression, beta/alpha globin mRNA ratio, and clinical severity of the beta-thalassemia patients. Ann Clin Lab Sci 44(2):189–193Google Scholar
- 15.Bhagat S, Patra PK, Thakur AS (2012) Association between XmnI polymorphism and HbF level in sickle cell disease patients from Chhattisgarh. Int J Biomed Sci 8(1):36–39Google Scholar