Heterozygosity for the C282Y Mutation in the Hemochromatosis Gene is Associated with Increased Serum Iron, Transferrin Saturation, And Hemoglobin in Young Women: A Protective Role Against Iron Deficiency?(Molecular Diagnostics and Genetics‪)‬

The high prevalence of iron deficiency and iron deficiency anemia (1, 2), especially in women of childbearing age, and its association with central nervous dysfunction (3-5), impaired work performance and response to exercise (6), impaired immune response (7), thermogenesis (8) and energy metabolism, and adverse outcome of pregnancy (9) represent a serious health problem. Worldwide, iron deficiency is the most common nutritional disorder. Women are more prone to suffer from the consequences of iron deficiency anemia because of menstrual blood loss and enhanced iron requirements during pregnancy and lactation, especially in developing countries (10). Genetic hemochromatosis (GH), a disorder that causes iron overload, is the most common autosomal recessive disorder, affecting 1 in 300 individuals in Northern European populations (11). Recently, mutations in the hemochromatosis (HFE) gene that are responsible for GH have been identified (12). A G-to-A transition at cDNA position 845 produces a substitution of tyrosine for a highly conserved cysteine residue at position 282 of the HFE protein. Homozygosity for this mutation has been found in 67-100% of patients with GH (12-17), and 3.2-13% of Caucasians have been found to be heterozygous for this gene alteration (12-17). Such a high prevalence of a single mutation is unusual for a disorder with an autosomal-recessive mode of inheritance. Analysis of microsatellites at the HFE gene locus revealed that the 282 mutation occurs on chromosomes with the same haplotype in different populations (18,19). This observation is a strong argument for a founder effect of the mutation arising on a single chromosome. The high frequency of this particular genetic defect may therefore be the result of a selection advantage for heterozygous carriers of this mutation. The metabolic consequences of the heterozygous state on iron metabolism may confer such a biological advantage. In the present study, the hypothesis was tested that the C282Y mutation in the HFE gene represents a protective factor against iron deficiency in young women.