Do mutations H63D and C282Y of the gene HFE influence the kinetics of iron metabolism in elite cyclist?
Authors: Duvallet Alain , Duvallet Emilie , Lhuissier François , Beaudry Michele 
Published: November 2023

The HFE gene provides instructions for producing a protein, located on the surface of cells, mainly on the liver and intestinal cells and on some immune system cells.

The patients homozygous for the C282Y or H63D mutation or compound heterozygote showed disorders with disrupted iron regulation and clinical expression of hereditary hemochromatosis. Patients heterozygous with a wild‐type gene don't present signs and symptoms.

It has been shown that many cyclists overtake iron because this one improves the performance, and that many sportsmen showed an hyperferritinemia. The question is “does this hyperferritinemia comes from the iron overtake or from a genetic predisposition?”

We studied 40 high level male cyclists with medical and nutrition history, and blood sampling (biochemical, hematological and genetic (HFE) analysis). Three groups were created: group 0 (wild‐type homozygote), −/−, group 1 mutation C282Y −/+; group 2 mutation H63D +/−.

Data were expressed as mean ± SEM. Student t tests (p < 0.05) assessed differences. All cyclists have continued iron and various vitamin supplementations. No one admitted to have been treated with erythropoietin. The median cumulative oral and parenteral iron intake were higher than the recommended daily intake (table 2) with higher values in cyclists without the HFE mutation.

If the hematocrit, the hemoglobin (Hb), the number of red cells or transferrin saturation (TS) are increased, their values stay in the normal upper limit in cyclists with or without mutation. Only the value for the ferritin is clearly increased (table 2). The comparison between groups 0 and 2 (heterozygous mutation H63D) doesn't show any statistical difference with values for ferritin, seric iron (SI) and TS tend to be increased in the second group. Between groups 0 and 1 (heterozygous mutation C282Y), significant differences are found for Hb, SI, TS and the capacity of transferrin (CS), with an increased ferritin. Between groups 1 and 2 no significant differences can be observed even if the transferrin and the CS are higher in group 2 and TS higher in group 1.

Present data confirm increased serum ferritin levels and excessive iron supplementation in elite cyclists, and indicate that the kinetics of iron metabolism with supplementation in iron and vitamin C uptake could be influenced by mutations which may lead to some metabolic modifications. The increases for SI, TS, and CS in the cyclists with mutations are accentuated in the group with the C282Y heterozygote mutation. If a sportsman inherits one abnormal gene, he won't develop hemochromatosis. But this must be responsible of an increase of the availability of iron.

The allelic frequency of C282Y and particularly H63D mutations is significantly increased in endurance sports (cycling, cross country and cross country skiing). As a result, mutations and iron uptake modify iron regulation; too much iron is absorbed from the diet, leading to an iron overload. This availability can promote performance in theses sports, in training and in competition.