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?

Genetic hemochromatosis (GH) is the most common autosomal-recessive disorde r (1 in 300 in populations of Celtic origin). Homozygosity for a C282Y muta tion in the hemochromatosis (HFE) gene is the underlying defect in similar to 80% of patients with GI-I, and 3.2-13% of Caucasians are heterozygous fo r this gene alteration. Because the high frequency of this mutation may res ult from a selection advantage, the hypothesis was tested that the C282Y mu tation confers protection against iron deficiency in young women. To addres s this question the genotype of codon 282 was determined in a cohort of 468 unrelated female healthcare workers, ages 18-40 years. In all study partic ipants, a complete blood count was obtained, and erythrocyte distribution w idth, serum iron, transferrin, transferrin saturation, and ferritin were me asured. Two individuals were homozygous for the C282Y mutation, 44 were het erozygous, and 416 were homozygous for the wild-type allele. Heterozygous w omen had significantly higher values for hemoglobin (P = 0.006), serum iron (P = 0.013), and transferrin saturation (P = 0.006) than women homozygous for the wild-type allele. Our data provide evidence for a protective role o f the C282Y mutation in the HFE gene against iron deficiency in young women and suggest that a more efficient utilization of nutritional iron may have contributed to the high prevalence of the mutation in Caucasian population s.