Bloody rust defends against plague.

[Rolanbek]

A peculiar condition Haemochromatosis which is characterised by the over absorption of iron into the blood may have given a competitive advantage in plague ridden areas.

In 1996 a mutation in HFE, which seemed to regulate the absorption of iron into the gut was found in those suffering from Haemochromatosis. Peculiarly interesting to epidemiologists is the counterintuitive finding that those which a faulty HFE gene far from having a high iron level in their macrophages, have an incredible low level of iron in these cells. This is important in inhibiting the attack by bacteria such as Yersinia pestis, (the plague) which will thrive inside Macrophages as long as there is sufficient iron for it to continue replicating. From there Yersinia hitches a ride to the lymph nodes were it goes on to form the plagues distinctive buboes.

So it may be no coincidence that Haemochromatosis is much more highly prevalent in areas that have suffered repeated plague pandemics.

This appears to be an analogue for the selective advantage conferred by sickle cell traits in malarial areas.

R

[The Fish]

Hi Rolanbek,
I was wondering if you were aware whether heterozygocity for the HFE mutation offers protection (as is the case for the sickle cell trait) or if only homozygotes have this? The reason I ask is that hereditary hemochromatosis (using the yankee spelling) is a result of homozygous inheritance of the HFE gene, and is a very serious disease. The over absorption of dietary iron results in deposition in various organs, including the heart and liver, leading to severe cardiac sequelae and liver disease. This would seem to be an overly high price to pay for plague protection. If, however, heterozygotes also have the effect, that would very effectively explain the persistence of the gene in the population.
Thanks!

[Rolanbek]

As the prevelence of the mutation in its heterozygous form is as high as 1 in 3 in some parts of northwest europe, that certainly implies some sickle cell style advantage.

In its Heterozygous form, which confers a slight increase in the levels of iron absorbed into the blood, and a slight reduction in macrophage iron levels, It has been shown that heterozygous carriers in mice have a partial resistance to TB, which also absorbs iron from Macrophages (university of cincinnati i think)

It may also explain why a surprising number of Haemochromatosis sufferers are repeat blood donors, even before diagnoses. Theraputic blood donation is often suggested as a way of managing the less severe versions of this mutation.

R

[The Fish]

It may also explain why a surprising number of Haemochromatosis sufferers are repeat blood donors, even before diagnoses. Theraputic blood donation is often suggested as a way of managing the less severe versions of this mutation.

I think you mean blood transfusion recipients? Both hemosiderosis and full-blown hemochromatosis are common problems in people who require repeat blood transfusions (hemophilia, thalassemias, etc.).

In any case, such a high prevalence of heterozygous individuals certainly does imply a protective function. Interesting!

[Rolanbek]

Definitely donors, most report reduction in the associated aches and pains that characterise the condition. Early stage and mild patients get a chance to consume some of their excess in the production of replacement haem groups.

This is exclusively in the case of hereditary sufferers not from those who acquire the condition through repeat transfusion for other conditions.

That aside Blood from heterozygotic donors is like gold dust at blood banks here, as it has fantastic levels of iron.


oh the Tb in mice trial was Oyebode Olakanmi, Larry S. Schlesinger and Bradley E. Britigan (Journal of Leukocyte Biology. 2007;81:195-204)

R

[The Fish]

Definitely donors, most report reduction in the associated aches and pains that characterise the condition. Early stage and mild patients get a chance to consume some of their excess in the production of replacement haem groups.

This is exclusively in the case of hereditary sufferers not from those who acquire the condition through repeat transfusion for other conditions.

That aside Blood from heterozygotic donors is like gold dust at blood banks here, as it has fantastic levels of iron.


oh the Tb in mice trial was Oyebode Olakanmi, Larry S. Schlesinger and Bradley E. Britigan (Journal of Leukocyte Biology. 2007;81:195-204)

R

Oh, right, I understand how blood donation can reduce iron levels, I thought you said in your previous post that these donors GOT hemochromatosis, which is the opposite. I misunderstood what you meant.

It's funny how many of these recessive diseases are protective in their heterozygous forms. Homozygous inheritance of the mutant CFTR gene, for instance, causes cystic fibrosis, but when only one copy is inherited, it's protective against typhoid. This is another of those mutant genes that's very common among people of Northern European descent. Epidemiology is really interesting.

[Rolanbek]

CFTR carriers also get advantages with cholera and TB.

Favism suffers also get the Malaria breaks that sickle cell carriers get.

I find the whole area fascinating.

R