Alpha-Hemoglobin Stabilizing Protein Gene Polymorphism (rs4499252 A/G) and its Association with Beta-Thalassemia Major in Iraqi Patients

Document Type : Original Articles

Authors

1 Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq

2 College of Medicine, University of Wasit, Wasit, Iraq

3 Shatra Technical College, Southern Technical University, Basra, Iraq

Abstract

Beta thalassemia (β-thalassemia) major is a genetic disorder of hemoglobin production that results in a diminished rate of synthesis of one or more of the globin chains causing variable degrees of anemia. Alpha-hemoglobin-stabilizing protein (AHSP) is a specific alpha-globin factor that affects the severity of the disease in patients with β-thalassemia. A recent study was conducted to investigate the polymorphism in the AHSP (rs4499252) gene and its association with β-thalassemia in Iraq. Blood samples were obtained from 90 β-thalassemia patients and 60 healthy individuals as a control group in the Wasit Center for Hereditary Anemia from August 2020 to January 2021. After DNA extraction from the whole blood, to determine the genotype of the AHSP gene, the High-Resolution Melt (HRM) Real-Time PCR was used. The results showed a significant increase (P<0.05) in genotype GG (wild type) of the SNP (rs4499252) in β-thalassemia patients, compared to the control group. On the other hand, genotype AA was significantly higher (P≤0.05) in β-thalassemia patients than in the control group, while the genotype GA showed a non-significant difference (P<0.01) between β-thalassemia patients and the healthy controls. The results also showed that the AHSP expression is a biomarker of hemoglobin H disease severity, and the A allele was more frequent in β-thalassemia patients than the G allele in Iraqi patients.

Keywords

References

  1. He L, Rockwood AL, Agarwal AM, Anderson LC, Weisbrod CR, Hendrickson CL, et al. Diagnosis of Hemoglobinopathy and beta-Thalassemia by 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry of Hemoglobin from Blood. Clin Chem. 2019;65(8):986-94.
  2. Ali EA, Albayati AA, Alshaban SA, Ali K. Serum Hepcidin and Ferritin Level Changes In Iraqi Adult Patients With Non-Transfusion Dependent Beta-Thalassemia Major And Intermedia. Int J Pharm Res. 2021;13(1).
  3. Samia HK, Ahmedy IA, Mahmoud A, Safaa IT. Role of alpha hemoglobin stabilizing protein expression in beta thalassemia patients. Med J Cairo Univ. 2018;86:4279-88.
  4. Iman A Ahmedy MD, Samia H Kandel MD, Safaa I Tayel MD, Mahmoud A El-Hawy MD. Role of Alpha Hemoglobin Stabilizing Protein Expression in Beta Thalassemia Patients. Med J Cairo Univ. 2018;86:4279-88.
  5. Gell D, Kong Y, Eaton SA, Weiss MJ, Mackay JP. Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein. J Biol Chem. 2002;277(43):40602-9.
  6. Kihm AJ, Kong Y, Hong W, Russell JE, Rouda S, Adachi K, et al. An abundant erythroid protein that stabilizes free alpha-haemoglobin. Nature. 2002;417(6890):758-63.
  7. Che Yaacob NS, Islam MA, Alsaleh H, Ibrahim IK, Hassan R. Alpha-hemoglobin-stabilizing protein (AHSP): a modulatory factor in beta-thalassemia. Int J Hematol. 2020;111(3):352-9.
  8. Cary N. Statistical analysis system, User's guide. Statistical. Version 9. SAS Inst Inc USA. 2012.
  9. Druml B, Cichna-Markl M. High resolution melting (HRM) analysis of DNA--its role and potential in food analysis. Food Chem. 2014;158:245-54.
  10. Pilon AM, Wong C, Garrett-Beal LJ, Weiss M, Gallagher PG, Bodine DM. Chromatin Remodeling of the Mouse AHSP Gene Requires EKLF. Blood. 2004;104(11):375.
  11. Perseu L, Giagu N, Sole G, Perra C, editors. AHSP expression in beta-thalassemia carriers with thalassemia intermedia phenotype. Blood; 2003: AMER SOC HEMATOLOGY 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA.
  12. Kong Y, Zhou S, Kihm AJ, Katein AM, Yu X, Gell DA, et al. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. J Clin Invest. 2004;114(10):1457-66.
  13. Bittles A, Erber W. Genotype-phenotype relationship in thalassemia: Predicting clinical severity by molecular testing. Genetics and population health conferences Western Australia, Australia: World Health Organization; Aug 8-10: Australia; 2004. p. 92.
  1. Bittles A, Erber W. Thalassemia genotype-phenotype correlations. Genetics and population health conferences Western Australia, Australia: World Health Organization; Aug 8-102004.
  2. Tanus-Santos JE, Desai M, Flockhart DA. Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics. 2001;11(8):719-25.
  3. Baudin-Creuza V, Vasseur-Godbillon C, Pato C, Prehu C, Wajcman H, Marden MC. Transfer of human alpha- to beta-hemoglobin via its chaperone protein: evidence for a new state. J Biol Chem. 2004;279(35):36530-3.
  4. Viprakasit V, Tanphaichitr VS, Chinchang W, Sangkla P, Weiss MJ, Higgs DR. Evaluation of alpha hemoglobin stabilizing protein (AHSP) as a genetic modifier in patients with beta thalassemia. Blood. 2004;103(9):3296-9.
  5. Mahmoud HM, Shoeib AA, Abd El Ghany SM, Reda MM, Ragab IA. Study of alpha hemoglobin stabilizing protein expression in patients with beta thalassemia and sickle cell anemia and its impact on clinical severity. Blood Cells Mol Dis. 2015;55(4):358-62.
Archives of Razi Institute
Volume 77, Issue 3 - Serial Number 3
May and June 2022
Pages 1033-1039

Files

Share

How to cite

Statistics