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Association of alpha hemoglobin–stabilizing protein (AHSP) gene mutation and disease severity among HbE—beta thalassemia patients

  • Rudra Ray
  • Siddhesh Arun Kalantri
  • Sunistha Bhattacharjee
  • Ankita Biswas
  • Aiman Shahab
  • Sujana Biswas
  • Maitreyee BhattacharyyaEmail author
Original Article
  • 26 Downloads

Abstract

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.

Keywords

Thalassemia Globin gene Transfusion Phenotype HbE beta thalassemia 

Abbreviations

NTDT

Non-transfusion-dependent thalassemia

TDT

Transfusion-dependent thalassemia

HPFH

Hereditary persistence of fetal hemoglobin

AHSP

Alpha hemoglobin–stabilizing protein

RBC

Red blood cells

Hb

Hemoglobin

HbF

Fetal hemoglobin

Notes

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.

Financial relationship

There is no financial relationship involved with the organization sponsored the research.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Rudra Ray
    • 1
  • Siddhesh Arun Kalantri
    • 2
  • Sunistha Bhattacharjee
    • 1
  • Ankita Biswas
    • 1
  • Aiman Shahab
    • 1
  • Sujana Biswas
    • 1
  • Maitreyee Bhattacharyya
    • 2
    Email author
  1. 1.Medical CollegeInstitute of Hematology and Transfusion MedicineKolkataIndia
  2. 2.Medical CollegeInstitute of Hematology and Transfusion MedicineKolkataIndia

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