XmnI POLYMORPHISM AND DISEASE SEVERITY IN PATIENTS WITH BETA THALASSEMIA FROM NORTHERN PAKISTAN

Tamoor Bin Hanif, Suhaib Ahmed, Jaleel Anwar, Syed Kazim Abbas Kazmi

Abstract


Background: Thalassemia is a heterogeneous disorder and several genetic factors influence the severity of thalassemia. An accurate and early diagnosis of a mild thalassemia genotype helps to avoid unnecessary transfusion and its complications. The aim of this study is to identify the association between XmnI polymorphism and disease severity in patients with β-thalassemia from northern Pakistan. Methods: The cross sectional study was conducted at the Department of Haematology, Armed Forces Institute of Pathology (AFIP) Rawalpindi, from September 2006 to June 2009. A total of 90 subjects including 30 with thalassemia major, 30 with thalassemia intermedia and 30 normal individuals were studied. DNA from each subject was tested for 15 β-thalassemia mutations and the presence of XmnI polymorphism using Amplification Refractory Mutation System and Restriction Fragment Length Polymorphism respectively. Results: One normal and one thalassemia major subject were found to be positive for homozygous and heterozygous XmnI polymorphism respectively. Among the thalassemia intermedia group, XmnI polymorphism was found in 12/30 patients, of whom 10 were homozygous and 2 were heterozygous for it. Conclusion: XmnI polymorphism is an important genotypic factor in Pakistani population for making a prospective diagnosis of thalassemia intermedia and predicting the severity of the disease.

Keywords: Thalassemia intermedia, XmnI endonuclease, Restriction Fragment Length Polymorphism, Northern Pakistan

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References


Hoppe CC. Newborn Screening for Hemoglobin Disorders.Hemoglobin 2011;35:556–64.

Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115:188–-92.

Gupta SK, Sharma M, Tyagi S, Pati HP.Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major. Indian J Pathol Microbiol 2011;54:609–11.

Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011;118:3479–88.

George E, Ann TJ. Genotype-phenotype diversity of beta-thalassemia in Malaysia: treatment options and emerging therapies.Med J Malaysia 2010;65:256–60.

Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int 2011;108:532–40.

Kohne E, Kleihauer E: Hemoglobinopathies in Germany—a longitudinalstudy over four decades. Dtsch Arztebl Int 2010;107:65–72.

Weatherall DJ: Hemoglobinopathies worldwide: Present and future.Curr Mol Med 2008;8:592–9.

Haj Khelil A, Morinière M, Laradi S, Khelif A, Perrin P, Ben Chibani J, Baklouti F. Xmn I polymorphism associated with concomitant activation of Gγ and Aγ globin gene transcription on a β0-thalassemia chromosome. Blood Cells Mol Dis 2011;46:133–8.

Karimi M, Yarmohammadi H, Farjadian S, Zeinali S, Moghaddam Z, Cappellini MD, Giordano PC. Beta-thalassemia intermedia from southern Iran: IVS-II-1 (G-->A) is the prevalent thalassemia intermedia allele. Hemoglobin 2002;26:147–54.

Qatanani M, Taher A, Koussa S, Naaman R, Fisher C, Rugless M,Old J,Zahid L. b-Thalassemia intermedia in Lebanon. Eur J Haematol 2000;64:237–44.

Tyagi S, Kabra M, Tandon N, Saxena1 R, Pati HP, Choudhry VP. Clinico-Haematological Profile of Thalassemia Intermedia Patients. Int J Hum Genet 2003;3:251–8.

Ahmed S, Anwar M. XmnI Ggamma-polymorphism in six unrelated Pakistani families with Inv/Del G gamma(A gammadeltabeta) degrees deltabeta-thalassemia. Am J Hematol 2005;80:303–5.

Ahmed S, Petrou M, Saleem M. Molecular genetics of beta-thalassemia in Pakistan: a basis for prenatal diagnosis. Br J Haematol 1996;94:476–82.

Ahmed S, Anwar M. Haematological and genetic features of deltabeta-thalassemia in Pakistan. J Coll Physicians Surg Pak 2006;16:19–22.

Taher A, Isma´eel H, Cappellini MD: Thalassemia intermedia: revisited. Blood Cells Mol Dis 2006;37:12–20.

Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of β thalassemia intermedia. Br J Haematol 2011;152:512–23.

Panigrahi I, Agarwal S, Pradhan M, Choudhry DR, Choudhry VP, Saxena R. Molecular characterization of thalassemia intermedia in Indians. Haematologica 2006;91:1279–80.

Ho PJ, Hall GW, Lou LY, Weatherall DJ, Thein SL. Beta-thalassemia intermedia: is it possible consistently to predict phenotype from genotype? Br J Haematol 1998;100:70–8.

Garewal G, Das R, Ahluwalia J, Marwaha RK, Varma S. Nucleotide -88 (C-T) promoter mutation is a common β-thalassemia mutation in the Jat Sikhs of Punjab, India. Am J Hematol 2005;79:252–6.

Schwarz C, Vetter B, Kohne E, Kulozik AE. Beta thalassemia in Germany: molecular genetics and clinical phenotype in immigrant and in the native population. Klin Padiatr 1997;209:172–7.


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