Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain

Abstract

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population.

Serum ferritin and transferrin saturation levels in β0 and β+ thalassemia patients

“…Therefore, due to the influence of these individuals in the composition of the Brazilian population, the co-inheritance findings of the mutations of the beta-globin gene with the H63D mutation reinforce the incidence of this mutation among the evaluated β 0 and Β + thalassemics. Homozygosity for C282Y and double heterozygosity for C282Y and H63D are frequently associated with ferritin increase and transferrin saturation, but for other genotypes, these metabolic alterations are less frequent (Aranda et al, 2010). The iron profile of heterozygous thalassemics with or without mutations in the HFE gene was similar, but due to the high occurrence of heterozygosity for H63D, our results mainly reflect the influence of this polymorphism in the observed ferritin concentration and transferrin saturation.…”

Paraoxonase-1 status in patients with hereditary hemochromatosis

“…Healthy volunteers were 95.7% wild-type homozygotes and 4.3% heterozygotes for the C282Y polymorphism of the HFE gene, and 63.4% were wild-type homozygotes, 32.3% heterozygotes, and 4.3% mutant homozygotes for the H63D polymorphism ( 20,21 ).…”

Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis

“…The risk of iron loading was higher when C282Y and H63D mutations coexist in HFE gene as a compound heterozygote (Beutler 2006;Aranda et al 2010). A gender effect on iron loading phenotypes in HFE mutations was noted with male gender having higher risks (Aranda et al 2010). Epigenetic factors and environmental factors such as dietary iron and alcohol also could play a role in determining the incidence of the disease.…”

“…Other genetic factors could include another mutation in the HFE gene and/or mutations in genes known to be involved in iron metabolism causing non-HFE hemochromatosis (Whitfield et al 2000;Lee et al 2004;Roetto et al 2003;Camaschella et al 2000). The risk of iron loading was higher when C282Y and H63D mutations coexist in HFE gene as a compound heterozygote (Beutler 2006;Aranda et al 2010). A gender effect on iron loading phenotypes in HFE mutations was noted with male gender having higher risks (Aranda et al 2010).…”

“…On the contrary, fruit juice excluding citrus fruits was demonstrated to be protective in hindering serum ferritin levels (Milward et al 2008). The presence of dietary calcium and fiber protected against iron loading (Aranda et al 2010). Thus, environmental or genetic factors likely influence the development of HH-related clinical symptoms (Olynyk et al 2005).…”