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