Bathum et al1 report an association of the C282Y/wt genotype with a shortened life expectancy. Although they are appropriately cautious in the interpretation of their results, the unwary reader may conclude that heterozygosity for this mutation may be harmful. However, it would be quite extraordinary for a common polymorphism such as the HFE C282Y mutation to have an adverse phenotypic effect. For a gene that decreases fitness in the homozygous state to reach a prevalence as high as is observed with the HFE mutations implies that heterozygotes have a selective advantage, not a disadvantage. Thus, one must resist the temptation to believe that the association that has been observed is one of cause and effect.
Beutler E, Felitti VJ. The C282Y Mutation Does Not Shorten Life Span. Arch Intern Med. 2002;162(10):1196-1197. doi: