HFE gene mutations and iron status of Brazilian blood donors

P.C.J.L Santos,C.S Chiattone,C.T Terada,E.M Guerra-Shinohara,R.D.C Hirata,S Rostelato,M.H Hirata,I Gonzales,R.D Cançado

doi:10.1590/s0100-879x2010000100015

Abstract

Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542) were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC) than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018) and a 83.65% decrease (P = 0.007) in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001) and the HFE 63HD plus DD genotype (55.84%, P = 0.021). In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

Highlights

Iron is essential for the adequate functioning of metabolic and structural proteins in cells
The genotype distribution for HFE gene mutation of female and male blood donors was in Hardy-Weinberg equilibrium. *Fisher exact, **chisquare, and ***Mann-Whitney tests were performed
The frequency of the HFE 282Y allele (2.1%, P > 0.05) was similar to that reported in studies conducted in healthy Brazilian individuals (1.1 to 1.4%) [14,15,16] and in blood donors from Colombia (1.8%) [24]

Summary

Introduction

Iron is essential for the adequate functioning of metabolic and structural proteins in cells. Proteins, such as HFE, hemojuvelin, transferrin receptor 2 (TFR2), and ferroportin, and a peptide called hepcidin, regulate iron metabolism. Mutations in the genes of these proteins or peptide are associated with the etiology of iron overload (hereditary hemochromatosis, HH), which is characterized by increased intestinal iron absorption and progressive accumulation of iron in the body [1]. The HFE protein forms a complex with β2-microglobulin and this complex can interact with transferrin receptor 1 (TFR1), decreasing its affinity for transferring and modulating iron absorption in enterocytes [2]. Higher frequencies of C282Y were found in individuals with HH, decreasing from Northern to Southern Europe, with the highest percentage occurring in Brittany (96%) [6] and the lowest in Italy (64%) [7] and Greece (39%) [8]

Objectives

Methods

Results

Conclusion