The Effect of Xmn -1 Polymorphism and Coinheritance of Alpha Mutations on Age at First Blood Transfusion in Iranian Patients with Homozygote IVS 1-5 Mutation
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Abstract
Background: Thalassemia syndromes are the most prevalent hereditary hemoglobinopathies in the world. Iran is located on the thalassemia belt. In this study, the effect of Xmn -1 polymorphism and coinheritance of alpha mutations on age at first transfusion as well as transfusion interval in Iranian thalassemic patients with homozygous Intervening Sequence (IVS) 1-5 mutation was assessed.
Materials and Methods: In this retrospective cross-sectional study, 154 transfusion-dependent thalassemia (TDT) patients (140 patients with β-thalassemia major and 14 cases with β-thalassemia intermedia) who were homozygote of IVS 1-5 mutation participated. Blood samples were collected from participants using EDTA containers for genomic DNA analysis. DNA extraction and amplification-refractory mutation to determine the Xmn -1 polymorphism were performed. Multiplex Polymerase Chain Reaction (PCR) was performed to identify alpha globin deletions.
Results: The mean age of participants was 29±7 years. Fifty-eight participants were male and 96 were female. A significant relationship between the presence of Xmn -1 polymorphism and age at receiving first transfusion was detected. Coinheritance of alpha thalassemia mutation did not have a significant effect on age at first transfusion or transfusion interval.
Conclusion: The presence of Xmn -1 polymorphism can delay the onset of transfusion in patients with homozygote IVS 1-5 mutation.
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3. Hashemieh M, Timori Naghadeh H,Tabrizi Namini M ,et al. The Iran Thalassemia Prevention Program: Success or Failure? Iran J Ped Hematol Oncol. 2015;5(3):161-6.
4.Najmabadi H, Karimi-Nejad R, Sahebjam S, et al. The β-thalassemia mutation spectrum in the Iranian population. Hemoglobin. 2001;25(3):285-96.
5.Bazi A, Miri-Moghaddam E. Spectrum of β-thalassemia Mutations in Iran, an Update. Iran J Ped Hematol Oncol. 2016;6(3):190-202.
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7.Rezaee AR, Banoei MM, Khalili E, et al. Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. Scientific World Journal. 2012;2012:635183.
8.Akhavan-Niaki H, Derakhshandeh-Peykar P, Banihashemi A, et al. A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population. Blood Cells Mol Dis. 2011;47(1):29-32.
9.Bohara V, Raut L, Badarkhe G, et al. Homozygosity for the severe β+-thalassemia Mutation [IVS-I-5 (G> C)] Causes the Phenotype of Thalassemia Trait: An Extremely rare presentation. Hemoglobin. 2013;37(1):101-5.
10.Aditya R, Verma IC, Saxena R, et al. Relation of Xmn-1 polymorphism & five common Indian mutations of thalassaemia with phenotypic presentation in β-thalassaemia. JK Science. 2006;8(3):139-43.
11.Said F, Abdel-Salam A. XmnI polymorphism: Relation to β-thalassemia phenotype and genotype in Egyptian Children. Egypt J Med Hum Genet. 2015; 16(2):123-7.
12.Dadheech S, Jain S, Madhulatha D, et al. Association of Xmn1− 158 γ G variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. Mol. Biol. Rep. 2014; 41(5):3331-7.
13.Miri-Moghaddam E, Bahrami S, Naderi M, et al. mn1-158 γ G variant in B-thalassemia intermediate patients in South-East of Iran. Int J Hematol Oncol Stem Cell Res. 2017;11(2):165-171.
14.Agouti I, Badens C, Abouyoub A, et al. Genotypic correlation between six common β-thalassemia mutations and the Xmn I polymorphism in the Moroccan population. Hemoglobin. 2007;31(2):141-9.
15.Motovali-Bashi M, Ghasemi T. Role of Xmn IG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate β-Thalassemia Patients. Iran Biomed J. 2015; 19(3): 177–182.
16.Thein SL, Wood WG, Steinberg MH, et al. The Molecular Basis of β Thalassemia, δβ Thalassemia, and Hereditary Persistence of Fetal Hemoglobin. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. 2nd ed. Cambridge: Cambridge University Press; 2009.
17.Winichagoon P, Fucharoen S, Chen P, et al. Genetic factors affecting clinical severity in β-thalassemia syndromes. J Pediatr Hematol Oncol. 2000;22(6):573-80.
18.Neishabury M, Azarkeivan A, Najmabadi H. Frequency of positive XmnI Gγ polymorphism and coinheritance of common alpha thalassemia mutations do not show statistically significant difference between thalassemia major and intermedia cases with homozygous IVSII-1 mutation. Blood Cells Mol Dis. 2010;44(2):95-9.
19.Yavarian M, Harteveld CL, Batelaan D, et al. Bernini LF, Giordano PC. Molecular spectrum of β-thalassemia in the Iranian province of Hormozgan. Hemoglobin. 2001;25(1):35-43.
20.Ansari SH, Shamsi TS, Ashraf M, et al. Molecular epidemiology of β-thalassemia in Pakistan: far reaching implications. Int J Mol Epidemiol Genet. 2011;2(4):403-8.
21. Shah PS, Shah ND, Ray HSP, et al. Mutation analysis of β-thalassemia in East-Western Indian population: a recent molecular approach. Appl Clin Genet. 2017;10:27-35.
22. Patel AP, Patel RB, Patel SA, et al. β-Thalassemia Mutations in Western India: Outcome of Prenatal Diagnosis in a Hemoglobinopathies Project. Hemoglobin. 2014; 38(5): 329-34.
23.Abuzenadah AM, Hussein IMR, Damanhouri GA, et al. Molecular basis of β- thalassemia in the western province of Saudi Arabia: identification of rare β- thalassemia mutations. Hemoglobin. 2011; 35(4): 346-57.
24. Baysal E. Molecular basis of β- thalassemia in the United Arab Emirates. Hemoglobin. 2011; 35(5-6): 581-8.
25. Hamamy HA, Al-Allawi NA. Epidemiological profile of common haemoglobinopathies in Arab countries. J Community Genet. 2013; 4(2): 147-67.
26.Saud AM, Al-Azzawie HF, Al-kazaz AA. Molecular study on β-Thalassemia Patients in Iraq. Curr Res Microbiol Biotechnol. 2013;1(4):160-5.
27. Hashemieh M, Azarkeivan A, Najmabadi H, et al. The Effect of Xmn1 Gene Polymorphism on Blood Transfusion Dependency and Hemoglobin Concentration among Iranian Thalassemia Patients with IVSII-1 Mutation. Iran. J. Pediatr. Hematol. Oncol. 2019;9(3):184-92.
28.Sharma N, Das R, Kaur J, et al. Evaluation of the genetic basis of phenotypic heterogeneity in north Indian patients with thalassemia major. Eur J Haematol. 2010;84(6):531-7.
29. Nemati H, Rahimi Z, Bahrami G. The Xmn1 polymorphic site 5' to the (G)gamma gene and its correlation to the (G)gamma:(A)gamma ratio, age at first blood transfusion and clinical features in beta-thalassemia patients from Western Iran. Mol Biol Rep. 2010 Jan;37(1):159-64.30.Tantawy AA, Andrawes NG, Ismaeil A, et al. Prevalence of Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major. Ann Saudi Med. 2012;32(5):487-91.
31.Oberoi S, Das R, Panigrahi I, et al. Xmn1-Gγ polymorphism and clinical predictors of severity
2.Cappellini MD, Viprakasit V, Taher AT. An overview of current treatment strategies for β-thalassemia. Expert Opin Orphan Drugs. 2014;2(7):665-79.
3. Hashemieh M, Timori Naghadeh H,Tabrizi Namini M ,et al. The Iran Thalassemia Prevention Program: Success or Failure? Iran J Ped Hematol Oncol. 2015;5(3):161-6.
4.Najmabadi H, Karimi-Nejad R, Sahebjam S, et al. The β-thalassemia mutation spectrum in the Iranian population. Hemoglobin. 2001;25(3):285-96.
5.Bazi A, Miri-Moghaddam E. Spectrum of β-thalassemia Mutations in Iran, an Update. Iran J Ped Hematol Oncol. 2016;6(3):190-202.
6. Orkin SH, Fisher DE, Ginsburg D, et al. Nathan and Oski’s Hematology of Infancy and Childhood, 8th ed. Philadelphia: Saunders; 2015.
7.Rezaee AR, Banoei MM, Khalili E, et al. Beta-Thalassemia in Iran: new insight into the role of genetic admixture and migration. Scientific World Journal. 2012;2012:635183.
8.Akhavan-Niaki H, Derakhshandeh-Peykar P, Banihashemi A, et al. A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population. Blood Cells Mol Dis. 2011;47(1):29-32.
9.Bohara V, Raut L, Badarkhe G, et al. Homozygosity for the severe β+-thalassemia Mutation [IVS-I-5 (G> C)] Causes the Phenotype of Thalassemia Trait: An Extremely rare presentation. Hemoglobin. 2013;37(1):101-5.
10.Aditya R, Verma IC, Saxena R, et al. Relation of Xmn-1 polymorphism & five common Indian mutations of thalassaemia with phenotypic presentation in β-thalassaemia. JK Science. 2006;8(3):139-43.
11.Said F, Abdel-Salam A. XmnI polymorphism: Relation to β-thalassemia phenotype and genotype in Egyptian Children. Egypt J Med Hum Genet. 2015; 16(2):123-7.
12.Dadheech S, Jain S, Madhulatha D, et al. Association of Xmn1− 158 γ G variant with severity and HbF levels in β-thalassemia major and sickle cell anaemia. Mol. Biol. Rep. 2014; 41(5):3331-7.
13.Miri-Moghaddam E, Bahrami S, Naderi M, et al. mn1-158 γ G variant in B-thalassemia intermediate patients in South-East of Iran. Int J Hematol Oncol Stem Cell Res. 2017;11(2):165-171.
14.Agouti I, Badens C, Abouyoub A, et al. Genotypic correlation between six common β-thalassemia mutations and the Xmn I polymorphism in the Moroccan population. Hemoglobin. 2007;31(2):141-9.
15.Motovali-Bashi M, Ghasemi T. Role of Xmn IG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate β-Thalassemia Patients. Iran Biomed J. 2015; 19(3): 177–182.
16.Thein SL, Wood WG, Steinberg MH, et al. The Molecular Basis of β Thalassemia, δβ Thalassemia, and Hereditary Persistence of Fetal Hemoglobin. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. 2nd ed. Cambridge: Cambridge University Press; 2009.
17.Winichagoon P, Fucharoen S, Chen P, et al. Genetic factors affecting clinical severity in β-thalassemia syndromes. J Pediatr Hematol Oncol. 2000;22(6):573-80.
18.Neishabury M, Azarkeivan A, Najmabadi H. Frequency of positive XmnI Gγ polymorphism and coinheritance of common alpha thalassemia mutations do not show statistically significant difference between thalassemia major and intermedia cases with homozygous IVSII-1 mutation. Blood Cells Mol Dis. 2010;44(2):95-9.
19.Yavarian M, Harteveld CL, Batelaan D, et al. Bernini LF, Giordano PC. Molecular spectrum of β-thalassemia in the Iranian province of Hormozgan. Hemoglobin. 2001;25(1):35-43.
20.Ansari SH, Shamsi TS, Ashraf M, et al. Molecular epidemiology of β-thalassemia in Pakistan: far reaching implications. Int J Mol Epidemiol Genet. 2011;2(4):403-8.
21. Shah PS, Shah ND, Ray HSP, et al. Mutation analysis of β-thalassemia in East-Western Indian population: a recent molecular approach. Appl Clin Genet. 2017;10:27-35.
22. Patel AP, Patel RB, Patel SA, et al. β-Thalassemia Mutations in Western India: Outcome of Prenatal Diagnosis in a Hemoglobinopathies Project. Hemoglobin. 2014; 38(5): 329-34.
23.Abuzenadah AM, Hussein IMR, Damanhouri GA, et al. Molecular basis of β- thalassemia in the western province of Saudi Arabia: identification of rare β- thalassemia mutations. Hemoglobin. 2011; 35(4): 346-57.
24. Baysal E. Molecular basis of β- thalassemia in the United Arab Emirates. Hemoglobin. 2011; 35(5-6): 581-8.
25. Hamamy HA, Al-Allawi NA. Epidemiological profile of common haemoglobinopathies in Arab countries. J Community Genet. 2013; 4(2): 147-67.
26.Saud AM, Al-Azzawie HF, Al-kazaz AA. Molecular study on β-Thalassemia Patients in Iraq. Curr Res Microbiol Biotechnol. 2013;1(4):160-5.
27. Hashemieh M, Azarkeivan A, Najmabadi H, et al. The Effect of Xmn1 Gene Polymorphism on Blood Transfusion Dependency and Hemoglobin Concentration among Iranian Thalassemia Patients with IVSII-1 Mutation. Iran. J. Pediatr. Hematol. Oncol. 2019;9(3):184-92.
28.Sharma N, Das R, Kaur J, et al. Evaluation of the genetic basis of phenotypic heterogeneity in north Indian patients with thalassemia major. Eur J Haematol. 2010;84(6):531-7.
29. Nemati H, Rahimi Z, Bahrami G. The Xmn1 polymorphic site 5' to the (G)gamma gene and its correlation to the (G)gamma:(A)gamma ratio, age at first blood transfusion and clinical features in beta-thalassemia patients from Western Iran. Mol Biol Rep. 2010 Jan;37(1):159-64.30.Tantawy AA, Andrawes NG, Ismaeil A, et al. Prevalence of Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major. Ann Saudi Med. 2012;32(5):487-91.
31.Oberoi S, Das R, Panigrahi I, et al. Xmn1-Gγ polymorphism and clinical predictors of severity
| Files | ||
| Issue | Vol 16, No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v16i1.8441 | |
| Keywords | ||
| Thalassemia; IVS 1-5 mutation; Xmn -1 polymorphism; Blood transfusion | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Hashemieh M, Saadatmandi Z, Azarkeivan A, Najmabadi H. The Effect of Xmn -1 Polymorphism and Coinheritance of Alpha Mutations on Age at First Blood Transfusion in Iranian Patients with Homozygote IVS 1-5 Mutation. Int J Hematol Oncol Stem Cell Res. 2022;16(1):47-54.
