Co-inheritance of alpha globin gene deletion lowering serum iron level in female beta thalassemia patients

  • Sayed AbdulAzeez
  • Noor B. Almandil
  • Zaki A. Naserullah
  • Sana Al-Jarrash
  • Ahmed M. Al-Suliman
  • Huda I. ElFakharay
  • J. Francis BorgioEmail author
Original Article


In the Eastern province of Saudi Arabia, thalassemia is highly common. Data on the effect of alpha globin gene variation on the concentration of iron on transfusion dependent Saudis are scanty. A total of 166 transfusions dependent β-thalassemia were included in this study to understand association between the alpha globin gene variation and concentration of iron. Using multiplex PCR, the alpha globin gene deletions were identified. Also, HBA1 and HBA2 genes were sequenced by Sanger sequencing. Saudi transfusion dependent female β-thalassemia patients with wild alpha globin genotype (αα/αα) were observed with iron level beyond the normal range. However, normal range of iron was observed in transfusion dependent Saudi female beta thalassemia patients co-inherited with double (-α3.7/-α3.7, or --Fil/αα or --MED/αα or - (α) 20.5/αα) or double heterozygosity (- -/-α3.7) alpha globin gene deletions, which is significantly (p < 0.0001) less compared to the Saudi transfused female with wild alpha globin genotype (αα/αα). The co-inheritance alpha globin gene deletions in female beta thalassemia patients were significantly lowering serum iron. Detailed studies can be taken forward to identify the molecular pathways involved in globin gene deletion as modulator.


3.7 deletion Alpha globin gene Thalassemia Saudi Arabia, iron load 



The authors thank The Dean, Institute for Research and Medical Consultations (IRMC), for her continuous support and encouragement and the administrative staff and facilities provided at IRMC, especially the technical assistance from Mr. Ranilo M. Tumbaga, Mr. Horace T. Pacifico, and Ms. Jee E. Aquino. This study was supported by The Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University (To JFB: 2012186 and 2014024; To SAA 2016-077-IRMC; 2014051), King Abdulaziz City for Science and Technology (To JFB LGP-35-204; and LGP-32-3) and National Science Technology and Innovation Plan (To JFB, Grant No: 12-MED 2798-46).

Compliance with ethical standards

Conflicts of interest

The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.


  1. 1.
    Cebrian FY, Flores MVR, Álvarez SI, Salinas IP, Iturrate CRV (2016) Combination of a triple alpha-globin gene with beta-thalassemia in a gypsy family: importance of the genetic testing in the diagnosis and search for a donor for bone marrow transplantation for one of their children. BMC Res Notes 9(1):220CrossRefGoogle Scholar
  2. 2.
    Akhtar MS, Qaw F, Borgio JF, Albuali W, Suliman A, Nasserullah Z, Al-Jarrash S, Al-Ali A (2013) Spectrum of α-thalassemia mutations in transfusion-dependent β-thalassemia patients from the Eastern Province of Saudi Arabia. Hemoglobin 37(1):65–73CrossRefGoogle Scholar
  3. 3.
    Hamamy HA, Al-Allawi NA (2013) Epidemiological profile of common haemoglobinopathies in Arab countries. J Community Genet 4(2):147–167CrossRefGoogle Scholar
  4. 4.
    Al-Nafie AN, Borgio JF, AbdulAzeez S, Al-Suliman AM, Qaw FS, Naserullah ZA, Al-Jarrash S, Al-Madan MS, Al-Ali RA, AlKhalifah MA, Al-Muhanna F (2015) Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients. Blood Cells Mol Dis 55(1):27–29CrossRefGoogle Scholar
  5. 5.
    Borgio JF, AbdulAzeez S, Naserullah ZA, Al-Jarrash S, Al-Ali RA, Al-Madan MS, Al-Muhanna F, Al-Suliman AM, Al-Nafie A, Steinberg MH, Al-Ali AK (2016) Mutations in the β-globin gene from a Saudi population: an update. Int J Lab Hematol 38(2):e38CrossRefGoogle Scholar
  6. 6.
    Borgio JF (2015) Molecular nature of alpha-globin genes in the Saudi population. Saudi Med J 36(11):1271CrossRefGoogle Scholar
  7. 7.
    Qadri MI, Islam SA (2000) Hemoglobin H disease in the eastern region of Saudi Arabia. Saudi Med J 21(7):666–671PubMedGoogle Scholar
  8. 8.
    AbdulAzeez S, Borgio JF (2016) In-silico computing of the most deleterious nsSNPs in HBA1 gene. PLoS ONE 11(1):0147702CrossRefGoogle Scholar
  9. 9.
    Neyshabouri M, Abbasi-Moheb L, Kahrizi K, Keyhany E, Najmabad H, Pourfath EA, Krugluger W, Oberkanins CH (2001) Alpha-thalassemia: deletion analysis in Iran. Arch Irn Med 4(4):160–164Google Scholar
  10. 10.
    Adekile AD, Haider MZ (1996) Morbidity, βS haplotype and α-globin gene patterns among sickle cell anemia patients in Kuwait. Acta Haematol 96(3):150–154CrossRefGoogle Scholar
  11. 11.
    Gilad O, Dgany O, Noy-Lotan S, Krasnov T, Elitzur S, Pissard S, Kventsel I, Yacobovich J, Tamary H (2014) Characterization of two unique α-globin gene cluster deletions causing α-thalassemia in Israeli Arabs. Hemoglobin 38(5):319–324CrossRefGoogle Scholar
  12. 12.
    Miri-Moghaddam E, Bahrami S, Naderi M, Bazi A, Karimipoor M (2016) Molecular characterization of β-thalassemia intermedia in southeast Iran. Hemoglobin 40(3):173–178CrossRefGoogle Scholar
  13. 13.
    Borgio JF, AbdulAzeez S, Al-Nafie AN, Naserullah ZA, Al-Jarrash S, Al-Madan MS, Al-Muhanna F, Steinberg MH, Al-Ali AK (2014) A novel HBA2 gene conversion in cis or trans:“α12 allele” in a Saudi population. Blood Cells Mol Dis 53(4):199–203CrossRefGoogle Scholar
  14. 14.
    El-Hazmi MA, Warsy AS (2001) Normal reference values for hematological parameters, red cell indices, HB A2 and HB F from early childhood through adolescence in Saudis. Ann Saudi Med 21(3/4):165–169CrossRefGoogle Scholar
  15. 15.
    Al-Assaf AH (2007) Anemia and iron intake of adult Saudis in Riyadh City-Saudi Arabia. Pak J Nutr 6(4):355–358CrossRefGoogle Scholar
  16. 16.
    Liu YT, Old JM, Miles K, Fisher CA, Weatherall DJ, Clegg JB (2000) Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. Br J Haematol 108(2):295–299CrossRefGoogle Scholar
  17. 17.
    Chow A, Ghassemifar R, Finlayson J (2013) Alpha thalassaemia due to non-deletional mutations on the-3.7 alpha globin fusion gene: laboratory diagnosis and clinical importance. Pathology 45(6):591–594CrossRefGoogle Scholar
  18. 18.
    Yamada KD, Tomii K, Katoh K (2016) Application of the MAFFT sequence alignment program to large data—reexamination of the usefulness of chained guide trees. Bioinformatics 32(21):3246–3251CrossRefGoogle Scholar
  19. 19.
    Baysal E (2011) α-Thalassemia syndromes in the United Arab Emirates. Hemoglobin 35(5–6):574–580. CrossRefPubMedGoogle Scholar
  20. 20.
    Olivieri NF, Brittenham GM (1997) Iron-chelating therapy and the treatment of thalassemia. Blood 89(3):739–761CrossRefGoogle Scholar
  21. 21.
    Al-Amodi AM, Ghanem NZ, Aldakeel SA, Ibrahim Al Asoom L, Rafique Ahmed N, Almandil NB, Naserullah ZA, Al-Jarrash S, Shakil Akhtar M, AbdulAzeez S, Al-Ali AK (2018) Hemoglobin A2 (HbA2) has a measure of unreliability in diagnosing β-thalassemia trait (β-TT). Curr Med Res Opin 34(5):945–951CrossRefGoogle Scholar
  22. 22.
    Borgio JF, AbdulAzeez S, Al-Muslami AM, Naserullah ZA, Al-Jarrash S, Al-Suliman AM, Al-Madan MS, Al-Ali AK (2018) KLF1 gene and borderline hemoglobin A2 in Saudi population. Arch Med Sci: AMS 14(1):230CrossRefGoogle Scholar
  23. 23.
    Borgio JF, Abdulazeez S, Almandil NB, Naserullah ZA, Al-Jarrash S, Al-Suliman AM, Elfakharay HI, Qaw FS, Alabdrabalnabi FI, Alkhalifah MA, Shakil Akhtar M (2018) The–α37 deletion in α–globin genes increases the concentration of fetal hemoglobin and hemoglobin A2 in a Saudi Arabian population. Mol Med Rep 17(1):1879–1884PubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Genetic Research, Institute for Research and Medical Consultation (IRMC)Imam Abdulrahman Bin Faisal UniversityDammamSaudi Arabia
  2. 2.Department of Clinical Pharmacy Research, Institute for Research and Medical Consultation (IRMC)Imam Abdulrahman Bin Faisal UniversityDammamSaudi Arabia
  3. 3.Dammam Maternity and Child HospitalDammamSaudi Arabia
  4. 4.King Faisal UniversityAl-AhssaSaudi Arabia
  5. 5.Almana General HospitalAl-KhobarSaudi Arabia

Personalised recommendations