HEME AND NONHEME IRON ABSORPTION IN HUMANS WITH C282Y AND H63D HFE MUTATIONS ASSOCIATED WITH HEMOCHROMATOSIS

Authors: Hunt, Janet; Zeng, Huawei

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/4/2003
Publication Date: 5/4/2003
Citation: Hunt, J.R., Zeng, H. 2003. Heme and nonheme iron absorption in humans with the C282Y and H63D mutations associated with hemochromatosis [abstract]. BioIron 2003 Symposium, May 4-9, 2003, Washington, D.C. Abstract #62. p.166.

Interpretive Summary:

Technical Abstract: The iron storage disorder hemochromatosis is commonly associated with homozygous C282Y mutations, and less frequently with compound heterozygous (C282Y and H63D) mutations in the HFE gene. Because of the relatively high frequency of HFE C282Y heterozygotes (~ 10%) among populations with Northern ancestry, the possibility of greater iron absorption by heterozygotes has implications for public health policies on food iron fortification. Before the specific mutation had been determined, Lynch et al. (1989) identified heterozygotes as children or siblings of hemochromatosis patients that shared a single HLA haplotype. These heterozygotes absorbed similar amounts of nonheme iron from a hamburger test meal, but more than twice as much nonheme iron from the same meal fortified with additional iron and ascorbic acid. We investigated whether C282Y heterozygotes absorb more iron, by measuring HFE C282Y and H63D mutations in DNA from buccal smears of 103 subjects in past radioiron absorption studies. Heme and nonheme iron absorption from experimental diets had been determined by labeling food with Fe-55 hemoglobin (from rabbit blood) and Fe-59 tracers. Isotope retention had been determined by measuring erythrocyte incorporation (both isotopes) and whole body scintillation counting (Fe-59 only) two weeks later. Duplicate DNA samples were genotyped using PCR with primers described by Feder (1996), digestion with endonuclease restriction enzymes, and electrophoresis to identify the C282Y and H63D mutations. H63D heterozygotes (n=24) did not differ from wildtypes (with neither mutation) in iron absorption, after adjusting for the logarithmic association of iron absorption with serum ferritin. Two compound heterozygotes absorbed heme iron similarly to wildtypes, and absorbed somewhat more nonheme iron than wildtypes when tested with a high bioavailability diet rich in meat and ascorbic acid, but not with a low bioavailability diet abundant in phytic acid and tannins. Five C282Y heterozygotes absorbed no more heme or nonheme iron from a high bioavailability diet. Consistent with published studies suggesting low phenotypic expression of the C282Y homozygous genotype, these limited data do not suggest generally greater heme or nonheme iron absorption from common diets by people heterozygous for the C282Y HFE mutation. We are in the process of prospectively testing heme and nonheme iron absorption from unfortified and fortified meals by 11 subjects genotyped as C282Y heterozygotes and their ferritin-matched wildtype controls.