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

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 a-thalassemia mutations and three polymorphic markers: the C→ T polymorphism at-158 of the Gc gene, the RFLP haplotype and the repeated sequence (AT)xTy in the b 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 b→-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. © 2013 Springer Science+Business Media Dordrecht.