1. ¹Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisbon, Portugal
2. ²Centro de Biopatologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal
3. ³Observatório Nacional de Saúde, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal

Correspondence: Paula Faustino, Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisbon, Portugal. Fax: +351-217526410. E-mail: paula.faustino@insa.min-saude.pt

Received 30 June 2004; Accepted 25 August 2004; Published online 5 November 2004.

Abstract

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in beta-thalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.