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

• Published in: Molecular biology reports Vol. 40; no. 11; pp. 6205 - 6212
• Main Authors: Jouini, L., Sahli, C. A., Laaouini, N., Ouali, F., Youssef, I. Ben, Dakhlaoui, B., Othmeni, R., Ouennich, F., Fredj, S. Hadj, Siala, H., Becher, M., Toumi, N. E., Fattoum, S., Hafsia, R., Bibi, A., Messaoud, T.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2013
• Subjects: Adolescent; Adult; alpha-Thalassemia - genetics; alpha-Thalassemia - metabolism; Animal Anatomy; Animal Biochemistry; beta-Globins - genetics; beta-Thalassemia - blood; beta-Thalassemia - diagnosis; beta-Thalassemia - genetics; Biomedical and Life Sciences; Child; Child, Preschool; gamma-Globins - genetics; Gene Order; Genetic Association Studies; Genetic Heterogeneity; Haplotypes; Hemoglobins - genetics; Hemoglobins - metabolism; Histology; Humans; Life Sciences; Middle Aged; Morphology; Mutation; Nucleotide Motifs; Phenotype; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Tunisia; Young Adult; Tunisia; Haplotypes; β-Thalassemia major; Mutations; Hemoglobinopathies; I polymorphism; β-Thalassemia intermedia
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-013-2732-y

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) x T y 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 Xmn I polymorphism. The regression analysis of combined genotypes (mutation/ Xmn I/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity ( p  < 0.05). Among the studied genotypes the Xmn I 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.