The C282Y mutation may have been positively selected as it mitigates the infertility of celiac disease.

Celiac disease and C282Y homozygous hemochromatosis have a similar increasing incidence across Europe. Both have gradients of frequency which increase from Turkey to North West Europe and culminate with a high frequency in Ireland. These two gradients follow the path of the Neolithic settlers who reached the edge of Europe at Ireland. Celiac disease and C282Y hereditary hemochromatosis have opposite effects on iron absorption and probably on the absorption of some other divalent metals including copper. The C282Y mutation is estimated to be some 2000 years old. Celiac disease is likely a much older disorder. The C282Y mutation may have been positively selected for as it increases absorption of divalent metal ions in celiac disease and thus has a mitigating effect on the infertility which may be associated with celiac disease.