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Genetics and Hemochromatosis

Hemochromatosis is a disorder in which the body fails to recognize that it has ingested enough iron, so it continues to absorb it rather than excrete the excess. Iron builds up and leads to joint damage, liver failure, heart failure, diabetes, arthritis and a range of other maladies. The gene causing the condition is relatively common in people of western European descent, perhaps one in four people have at least one copy of the gene. It might have originated as a mechanism for minimizing iron deficiencies among undernourished people.

But why would a gene that causes so many serious disorders have survived in a population?

Having access to iron helps bacteria grow and multiply in a host, and it is well known that anemic infants tend to be less susceptible to infection. To counter infection, the human body can sequester its iron, making it unavailable to the invading pathogens. One mechanism is via proteins that chelate the iron, locking it up, and another occurs in the acute phase response of the immune system. One would think that, because people with hemochromatosis have an excess of iron, they would be particularly susceptible to infection. But curiously, an exception lies in their macrophages, which have less iron than a normal person’s. So when a normal person’s macrophages encounter an invading pathogen, the pathogen can use the iron in the white blood cells to grow, later spreading the infection through the lymphatic system. In a person with hemochromatosis the lower iron content of the macrophages helps them to stifle infections before they take hold.

The bubonic plague afflicted Europe for centuries, but one of the best documented outbreaks was the Black Death, which began around 1347, killing between 30 and 50% of populations where it spread - a total of around 25 million people. There were many subsequent, smaller outbreaks down the centuries. The plague particularly affected healthy males; the elderly and women tended to be malnourished and so had iron deficiencies and susceptibility appears to mirror the level of iron in the victim’s body. Because of their resistance to infection, Moalem hypothesized that young males with the hemochromatosis mutation experienced lower mortality during the Black Death and lived to reproductive age, thus spreading the mutation through the population, even though it can have adverse consequences in later life.

As a side-bar, phlebotomy is an effective treatment for hemochromatosis; it immediately reduces the iron in the patient’s system and counters the iron build-up. This lends some credence to the age-old therapy of blood letting, although this was used for a wide range of conditions, for many of which it was almost certainly counter-productive.

(Sharon Moalem. Survival of the sickest: the surprising connections between disease and longevity. Harper Collins, 2007)