Factors regulating Hb F synthesis in thalassemic diseases

Fabrizio Mastropietro¹ , Guido Modiano² , Maria Pia Cappabianca¹ , Enrica Foglietta¹ , Carmelo D'Asero³ , Mauro Mezzabotta¹ , Donatella Ponzini¹ , Laura Maffei¹ , Antonio Amato¹ , Maria Lerone¹ , Paola Grisanti¹ , Paola Di Biagio¹ , Silvana Rinaldi¹ and Ida Bianco¹

¹Associazione Nazionale per la lotta contro Ie Microcitemie in Italia, Rome, Italy

²Dipartimento di Biologia, Università Tor Vergata, Rome, Italy

³Ospedale San Pietro-Fatebenefratelli, Rome, Italy

author email corresponding author email

BMC Blood Disorders 2002, 2:2doi:10.1186/1471-2326-2-2


Published:	6 February 2002

Abstract

Background

The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters.

Materials and Methods

Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls.

Results

Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta⁺ thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major.

Conclusions

The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients.