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Role of XmnI restriction site polymorphism and JAK2 gene mutation in β-Thalassemia

Author Affiliations

  • 1 Department of Biotechnology, DVR & HS MIC College of Technology, Kanchikacherla, AP, INDIA

Int. Res. J. Biological Sci., Volume 2, Issue (1), Pages 41-45, January,10 (2013)

Abstract

-Thalassemia is one of the most prevalent hereditary disorder in the world. It is the most common hemoglobin disorder found in the Indian sub continent, caused by point mutations or more rarely deletions in the -globin gene on chromosome 11, leading to reduced () or absent () synthesis of the chains of hemoglobin (Hb). The objective of this study is to understand the role of modifier genes and their polymorphic forms in amelioration or deterioration of the disease and severity of -thalassemias. The XmnI polymorphic site was determined by PCR-RFLP procedure. The XmnI restriction site at -158 position of the -gene is associated with increased expression of the -globin gene and higher production of HbF. The levels of and chains were detected by HPLC. JAK2 V617F mutation indicate the phenotypic variations and for predicting the risk of major clinical events. In allele specific polymerase chain reaction (PCR) V617F mutation independently predicted the evolution toward large splenomegaly.

References

  1. Flint J., Harding RM., Boyce AJ. and Clegg JB., The population genetics of the haemoglobinopathies, Bailliere's Clin Haematol, 11(1), 1-51 (1998)
  2. Huisman THJ., Carver MFH., The beta and delta thalassemia repository, Hemoglobin22, 169-95 (1998)
  3. Schrier S.L., Pathobiology of thalassemic erythrocytes, Current Opinion in Hematology, 7578 (1997)
  4. Olivieri N., The b-thalassemias, New England Journal of Medicine, 341, 99109 (1999)
  5. Angastiniotis M. and Modell B., Global epidemiology of hemoglobin disorders, Ann N Y Acad Sci., 850, 251-69 (1998)
  6. Varawalla NY., Old JM., Sarkar R., Venkatesan R. and Weatherall Dj., The spectrum of beta thalassemia mutations on the Indian subcontinent: the basis for prenatal diagnosis, British J Hematology, 78, 242-247 ( 1991)
  7. Thein S.L. and Wainscoat J.S., Association of thalassaemia intermedia with a -globin gene haplotype, Br J Haematol,65(3), 367-373 (1987)
  8. George E., A Practical algorithm to screen for thalassaemia: BHESZ+F protocol, Malaysian Journal of Medicine and Health Sciences, 3(1), 1 (2007)
  9. Wilson J.B., Headlee M.E. and Huisman T.H.J., A new high performance liquid chromatographic procedure for the separation and quantitation of various hemoglobin variants in adults and newborn babies, J Lab Clin Med, 102, 17485 (1983)
  10. Rogers B.B., Wessels R.A., Ou C.N. and Buffone G.J., High performance liquid chromatography in the diagnosis of hemoglobinopathies and thalassemias, Am J Clin Pathol, 84, 6714 (1985)
  11. Fessas P., Stamatoyannopoulos G.A. and Karaklis A., Hemoglobin Pylos: Study of a hemoglobinopathy resembling thalassemia in heterozygous, homozygous and double heterozygous state, Blood, 19, 1-22 (1962)
  12. Cao A GR., Beta-Thalassemia, Gene Reviews, (2005)
  13. Ronald Hoffman Hematology, Basic Principles and Practices 4th edition, Elsevier Churchill Livingstone, (2005)
  14. Thein SL., Genetic insights into the clinical diversity of beta thalassaemia, Br J Haematol, 124(3), 264-74 (2004)
  15. Taher A., Isma'eel H. and Cappellini MD., Thalassemia intermedia: revisited, Blood cells, molecules and diseases, 37(1), 12-20 (2006)
  16. Phadke SR. and Agarwal S., Phenotype score to grade the severity of thalassemia intermedia, Indian J Pediatrics, 70(6), 477-81 (2003)
  17. Rund D. and Rachmilewitz E., Beta-thalassemia, New Eng J Med, 353(11), 1135-46 (2005)
  18. Weatherall DJ. and Clegg JB., The Thalassemia Syndromes. 4th ed. Oxford: Blackwell Scientific Publications, (2001)
  19. Verma IC., Choudhry VP. and Jain PK., Prevention of thalassemia: A necessity in India, Indian J Pediatr, 59, 649-654 (1992)
  20. Rees DC., Porter JB., Clegg JB. and Weatherall DJ., Why are hemoglobin F levels increased in HbE/beta thalassemia, Blood, 94, 3199-3204 (1999)
  21. Fucharoen S., Siritanaratkul N. and W inichagoon P., Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia/hemoglobin E disease, Blood, 87, 887-92 (1996)
  22. Gilman JG. and Huisman THJ., DNA sequence variation associated with elevated fetal Gg globin production, Blood, 66, 783-87 (1985)
  23. De Domenico I., Lo E., Ward DM. and Kaplan J., Hepcidin-induced internalization of ferroportin requires binding and cooperative interaction with Jak2, Proc Natl Acad Sci., 106(10), 38005 (2009)
  24. Libani IV., Guy EC. and Melchiori L., Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in -thalassemia, Blood, 112(3), 875885 (2008)
  25. Mamatani M., Jawahirani A., Das K., Rughwani V. and Kulkarni H., Bias-corrected diagnostic performance of the naked-eye single-tube red-cell osmotic fragility test (NESTROFT): an effective screening tool for beta-thalassemia, Hematology, 11(4), 277-86 (2006)
  26. Old JM., Varawalla NY. and Weatherall DJ., The rapid detection and pre-natal diagnosis of thalassemia in the Asian Indian and Cypriot populations in the UK, Lancet, 336, 834 837 (1990)
  27. Baxter EJ., Scott LM., Campbell PJ., East C., Fourouclas N. and Swanton S., Cancer Genome Project, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders, Lancet, 365, 1054-6 (2005)
  28. Dedoussis GV., Mandilara GD., Boussiv M. and Loutradis A., HbF production in b-thalassaemia heterozygotes for the IVSII-1 G-A 0-globin mutation, Implication of the haplotype and the Gg-158 C-T mutation on the HbF level, Am J Hematol, 64, 151-55 (2000)