Hemochromatosis and its victory over natural selection

Hemochromatosis is a hereditary disease, where the body builds up excessive levels of iron. The condition affects 1:200 people and 1:4 are carriers of the allele in the UK. The condition has been described as ‘the Celtic curse’, due to the increased frequency of the disorder within the white, western Europeans. Symptoms include: fatigue, joint pain, erectile dysfunction, amenorrhea and arrhythmia. It is generally diagnosed between the ages of 30-50. The possible consequences if left untreated include: damage to organs including Cirrhosis, Liver cancer and heart failure. The typical treatment involves regular phlebotomy, historically known as bloodletting. Avoiding iron or vitamin C supplements and alcohol is recommended. [1]

How has the gene been able to overcome natural selection?

Iron is needed by the body to form haem groups, which is essential for the transport of oxygen to respiring cells. Iron forms the cofactor of many metabolic enzymes and many dieticians originally took the opinion the more iron the better. However, extreme iron concentrations enhance the functioning of parasites. The body uses Chelators as the first line of defence to counteract the ability of parasites to use our iron stores.

It is thought that the survival of hemochromatosis allele dates back to the era of the bubonic plague. Those people with iron rich diets were particularly susceptible to the disease as the bacterium thrived off their iron in the macrophages. Hemochromatosis disrupts the distribution of iron and starves macrophages. Therefore, this long term life threatening illness became a short term advantageous adaption against bubonic plague.2

A study from the New England Journal of Medicine has linked hemochromatosis with being taller. For example, Swiss males with hemochromatosis have been found to be approximately 4.3 cm taller. In the past, added height has been a selective pressure which allowed the mutated gene to persevere through generations of natural selection. [2]

People with hemochromatosis are better able to survive on low iron diets. This would have benefitted, Hunter-Gatherers who had irregular and unpredictable sources of iron. People who had severe blood losses such as women in childbirth and young warrior males, had better chances of surviving, which made hemochromatosis a positive selection factor. Due to menstruation, women experience the effects of hemochromatosis later in life, particularly after menopause. Therefore, this would not affect genetic selection, as the woman no longer reproduced.

The link between Hemochromatosis and colon cancer

Hemochromatosis is caused by a recessive allele on the gene HFE, which codes for a transmembrane protein which has a role in iron homeostasis. Although the condition was first identified in 1865, the HFE gene was not identified until 1996.[3] The association between liver cancer and hemochromatosis has previously been well documented. In a recent study, scientists concluded that those with the HFE mutation have an increased colon cancer risk and is greater in carriers who are older or consume high quantities of iron. The study factored in other environmental influences such as age, race, sex, red meat consumption, previous family history of colon cancer. The mechanism for this association is unclear, but it’s suggested that excess iron ‘may promote increased oxidative stress and induce DNA damage’ but also, that iron allows the proliferation of tumor growth.[4]

 

 

[1] NHS. Hemochromatosis. http://www.nhs.uk/conditions/Haemochromatosis/Pages/Introduction.aspx

2Stephen Cobb. Hemochromatosis tall tales and the HFE gene. http://celticcurse.org/hemochromatosis-tall-tales-and-the-hfe-gene/

3 Dr. Sharon Moalem. Survival of the Sickest. Chapter 1: Ironing it out.

4 http://jnci.oxfordjournals.org/content/95/2/154.full

 

 

 

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