The Impact of BCL11A and HBS1L-MYB Polymorphic Markers in Affected and Carriers of Beta Thalassemia with High Level of Fetal Hemoglobin in South of Iran, Khuzestan

Document Type : Original Article

Authors

1 Narges Medical Genetics & PND Laboratory, Ahvaz ,Iran

2 Assistant Professor of Molecular Medicine.Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

3 Master of Science in Molecular Medicine.Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

4 Professor of Genetic.Department of Medical Genetic, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

5 Associate Professor of Genetic.Department of Medical Genetic, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

6 Associate Professor of Endocrinology. Laboratory of Genetic Medicine and Prenatal Diagnosis, Narges, Ahvaz, Iran.

Abstract

Background and Objective: The increase of HbF in some beta-thalassemia and sickle cell patients ameliorates the disease severity. Therefore, understanding the reasons behind the increasing of fetal hemoglobin is needful. The molecular explanation of fetal hemoglobin increment might be correlated with the genes which play a regulatory role in expression of beta-globin cluster genes. In this study, the likelihood of polymorphisms of BCL11A and HBS1L-MYB regions to cause HbFelevation was studied.
Subjects and Methods: In this investigation, 50 thalassemia patients with high level of fetal hemoglobin and 50 healthy individuals as control group were selected from Khuzestan. The allele frequency of rs28384513, rs766432, rs11886868 and rs4895441 polymorphisms were assessed by using PCR-RFLP and PCR- sequencing methods.
Results: The frequency of C allele in rs766432 (A/C), C allele in rs11886868 (C/T) and A allele in rs28384513 (A/C) were significantly high among the patients with increased level of HbF. Whereas, the frequency of rs4895441 (A/G) polymorphism had no significant differences compared with the patients with high level of HbF and control group.
Conclusion: Based on this study, rs766432 (A/C), rs11886868 (C/T) and rs28384513 (A/C) polymorphisms are correlated with HbF increased and they can be used to predict the clinical features of fetus in case of bearing the major or intermediate forms of thalassemia. However, to confirm these results these markers need to be studied by applying a larger number of samples.

Keywords

References

1-Fabrice Danjou, Franco Anni, Renzo Galanello. Beta-thalassemia: from genotype to phenotype Haematologica 2011;96(11):1573-5.
2-Thein, S. L. and Menzel, S. Discovering the genetics underlying foetal haemoglobin production in adults. British Journal of Haematology 2009;145(4): 455-67.
3-Hamid M, Mahjoubi F, Akbari MT, Arab A, Zeinali S, Karimipoor M. Molecular analysis of gamma-globin promoters, HS-111 and 3'HS1, in beta-thalassemia intermedia patients associated with high levels of Hb F. Hemoglobin 2009;33(6):428-38.
4-Thein S L. 'Beta-thalassaemia prototype of a single gene disorder with multiple phenotypes. International Journal of Hematology 2002;76: 96-104.
5-Menzel S, Garner C, Gut I, Matsuda F, Yamaguchi M, Heath S, et al. A QTL influencing F cell production maps to a gene encoding a zincfinger protein on chromosome 2p15. Nature Genetics 2007; 39(10):1197-9.
6-Farrell JJ, Sherva RM, Chen ZY, Luo HY, Chu BF, Ha SY, et al. A 3-bp deletion in the hbs1l-myb intergenic region on chromosome 6q23 is associated with hbf expression. Blood 2011;117:4935-4945.
7-Wahlberg K, Jiang J, Rooks H, Jawaid K, Matsuda F, Yamaguchi M, et al. The hbs1l-myb intergenic interval associated with elevated hbf levels shows characteristics of a distal regulatory region in erythroid cells. Blood 2009;114:1254-1262.
8-Wallrapp C, Verrier SB, Zhouravleva G, Philippe H, Philippe M, Gress TM, et al. The product of the mammalian orthologue of the Saccharomyces cerevisiae HBS1 gene is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity. FEBS Letters 1998; 440: 387-392.
9-Westin EH, Gallo RC, Arya SK, Eva A, Souza LM, Baluda MA, et al. Differential expression of the amv gene in human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 1982;79 (7): 2194-8.
10- Makani J, Menzel S, Nkya S, Cox SE, Drasar E, Soka D, et al. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia. Blood 2011;117(4):1390-2.
11- Thein SL, Menzel S, Peng X, Best S, Jiang J, Close J, et al. Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proceedings of the National Academy of Sciences of the United States of America 2007;104 (27), 11346-51.
12- Sedgewick AE, Timofeev N, Sebastiani P, So JC, Ma ES, Chan LC, et al.BCL11A is a major HbF quantitative trait locus in three different populations with betahemoglobinopathies. Blood Cells Molecules and Disease 2008;41(3):255-8.
13- Thi Khanh Tien Nguyen, Philippe Joly, Claire Bardel, Mustapha Moulsma, Nathalie Bonello-Palot, Alain Francina. The XmnI (G)gamma polymorphism influences hemoglobin F synthesis contrary to BCL11A and HBS1L-MYB SNPs in a cohort of 57 beta-thalassemia intermedia patients. Blood Cells Molecules and Diseases 2010 45(2):124-7.
14- Hashemi Gorji F, Hamid M, Arab A,, Amirian A, Zeinali S, Karimipoor M. Relationship between DNA polymorphisms at the BCL11A and HBS1L-MYB loci in 9-Thalassemia patients with increased fetal hemoglobin levels. Scientific Journal of Iran Blood Transfus Organ 2011;8(3):149-157.
15-Neishabury M, Zamani F, Keyhani E, Azarkeivan A, Abedini SS, Eslami MS, et al. The influence of the BCL11A polymorphism on the phenotype of patients with beta thalassemia could be affected by the beta globin locus control region and/or the Xmn1-HBG2 genotypic background. Blood Cells Molecules and Diseases 2013;51(2):80-4.
16-Ngo D, Bae H, Steinberg MH, Sebastiani P, Solovieff N, Baldwin CT, et al. Fetal hemoglobin in sickle cell anemia: genetic studies of the Arab-Indian haplotype. Blood Cells, Molecules and Diseases 2013;51(1):22-6.
Jundishapur Scientific Medical Journal
Volume 16, Issue 6 - Serial Number 111
January and February 2018
Pages 611-619

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History

  • Receive Date: 11 July 2017
  • Revise Date: 22 November 2017
  • Accept Date: 25 December 2017

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