Studio del gene AHSP nelle β-Talassemie

Objective: To establish whether AHSP might have a role in modifying the clinical severity of beta-thalassemia. Background: The severity of beta-thalassemia reflects the degree of globin chain imbalance and the excess of free alpha-globin chains that precipitate and cause oxidative damage in red cell precursors, inducing their premature destruction (ineffective erythropoiesis). AHSP is an abundant erythroid-specific protein that binds specifically to free alpha-globin and prevents its precipitation in vitro. It has been demonstrated in the animal model that AHSP is required for normal haemoglobin production and that it acts as a chaperone, to prevent the harmful aggregation of alpha-globin during normal erythroid development and in diseases with globin chain imbalance. Patients and methods: AHSP gene (~1.4 Kb) and its promoter region was directly sequenced from PCR amplified DNA on ABI PRISM 3100, in 19 thalassemia intermedia and 14 thalassemia major patients with similar genetic characteristics (beta39/beta39, 3 or 4 alpha-globin genes and I-II or II-II haplotype according to Orkin et al). Results: No nucleotide mutation that might alter the structure and function of AHSP was identified. We found in the large majority of the cases the same haplotypes with the same frequencies described in S/E Asia (Viprakasit et al., Blood 2004). No difference has been found in the haplotype frequencies between the beta-thalassemia major and intermedia patients. Conclusion: We did not find mutations or specific association between haplotype of AHSP and disease severity in these patients, suggesting that AHSP is not a disease modifier in Sardinian beta-thalassemia patients.