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Association between beta globin haplotypes, HBBP1 and HMOX1 polymorphisms in relation to HbF among sickle cell anemia patients: a study in Southwest Iran

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Abstract

The haplotypes of β-globin gene cluster in patients with sickle cell anemia are associated with different clinical manifestations and fetal hemoglobin (HbF) levels. In addition, SNP in some genes within the β-globin gene cluster (HBBP1) and outside it (HMOX1) has been recently reported to be related to HbF levels. In this study, rs2071348 and rs2071746 polymorphisms in HBBP1 and heme oxygenase 1 (HMOX1) genes associated with different haplotypes and HbF levels in patients with sickle cell anemia were evaluated in comparison with healthy subjects. In this case-control study, 150 patients with sickle cell anemia (90 homozygous and 60 sickle-cell trait) were evaluated and compared with 50 healthy individuals referred to Shafa tertiary hospital in Ahvaz city of Khuzestan Province, Iran. HbF level was measured by alkali and acid electrophoresis. PCR-RFLP and ARMS-PCR methods were used to determine β-globin gene haplotypes and HBBP1 gene polymorphism, respectively. Arab-Indian was the most common genotype found in both homozygous and sickle-cell trait patients with a respective prevalence of 55.5 and 50% followed by homozygous Benin with 11.1 and 18.3% prevalence, respectively. The highest and lowest level of HbF were observed in Arab-Indian (24.1 ± 6.35) and Benin/Benin haplotypes (7.63 ± 2.29), respectively. A significant relationship was found between HbF level with rs2071746 A>T polymorphism of HMOX1 gene (P < 0.019) as well as with rs2071348 polymorphism of HBBP1 gene (P < 0.034). However, there was no significant relationship between haplotypes with gene polymorphisms. Arab-Indian was the most common haplotype in this region. The HbF level was significantly higher in patients with Arab-Indian haplotype, patients with C genotype in rs2071348 polymorphism locus of HBBP1 gene, and patients with T genotype in rs2071746 polymorphism locus of HMOX gene.

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Acknowledgments

This paper is issued from the thesis of Abolfazl Ramezani, MSc student of hematology and blood banking. This work was financially supported by grantIR. AJUMS.REC.TH 93/15 from vice chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences.

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Authors and Affiliations

  1. Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Kaveh Jaseb, Abolfazl Ramezani, Mohammad Ali Jalali Far, Abbas Khosravi & Najmaldin Saki

  2. Department of Medical Genetics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Javad Mohammadi-Asl

Authors
  1. Kaveh Jaseb
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  2. Abolfazl Ramezani
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  3. Mohammad Ali Jalali Far
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  4. Javad Mohammadi-Asl
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  5. Abbas Khosravi
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  6. Najmaldin Saki
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Contributions

N.S. has conceived the manuscript and revised it. A.R., N.S., and A.Kh. wrote the manuscript; M.A.J. and K.J. provided clinical data and information. N.S. and J.M.A. performed the technical tests.

Corresponding author

Correspondence to Najmaldin Saki.

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Ethical approval

All the procedures performed in the studies involving human participants were in accordance with the ethical standards of local ethics committee of the Ahvaz Jundishapur University of Medical Sciences as well as 1964 Helsinki declaration. Written informed consent was obtained from all patients and normal subjects.

Conflict of interest

The authors declare that they have no conflict of interest.

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Highlights

• HbF levels may be influenced by genetic modifiers.

• Arab-Indian haplotype can be associated with higher HbF levels.

• Benin Indian haplotype can be associated with lower HbF levels.

• The presence of HBBP1 C and HMOX1 T polymorphism can be associated with higher HbF levels.

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Jaseb, K., Ramezani, A., Far, M.A.J. et al. Association between beta globin haplotypes, HBBP1 and HMOX1 polymorphisms in relation to HbF among sickle cell anemia patients: a study in Southwest Iran. Comp Clin Pathol 26, 1149–1155 (2017). https://doi.org/10.1007/s00580-017-2500-9

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  • DOI: https://doi.org/10.1007/s00580-017-2500-9

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