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Association between clinical expression and molecular heterogeneity in β-thalassemia Tunisian patients

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Abstract

Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between β-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at −158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)xTy in the β globin silencer, in two groups of β-thalassemia major and β-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to β+ −87 (C → G), −30 (T → A) and IVSI-6 (T → C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity (p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the β-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of β-thalassemia that would be responsible of clinical variability.

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Acknowledgments

This work has been supported by the Ministry of scientific research and technology and competence development (LR2000 Lab Sante′-01).

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Authors and Affiliations

  1. Biochemistry Laboratory (Research Laboratory “Haemoglobinopathies and Cystic Fibrosis), Children’s Hospital, Lab Santé 01”, Bab Saadoun Square, 1007, Tunis, Tunisia

    L. Jouini, C. A. Sahli, N. Laaouini, F. Ouali, I. Ben Youssef, B. Dakhlaoui, R. Othmeni, F. Ouennich, S. Hadj Fredj, H. Siala, M. Becher, N. E. Toumi, S. Fattoum, R. Hafsia, A. Bibi & T. Messaoud

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  1. L. Jouini
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  2. C. A. Sahli
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  3. N. Laaouini
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  15. A. Bibi
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Correspondence to A. Bibi.

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Jouini, L., Sahli, C.A., Laaouini, N. et al. Association between clinical expression and molecular heterogeneity in β-thalassemia Tunisian patients. Mol Biol Rep 40, 6205–6212 (2013). https://doi.org/10.1007/s11033-013-2732-y

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  • DOI: https://doi.org/10.1007/s11033-013-2732-y

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