Cholera

Question

Is it true that a CF person is more resistant to cholera and in earlier days plague?

Answer

CF is caused by mutations in the CFTR gene. Every individual has 2 CFTR genes and CF patients carry mutations on both CFTR genes. Some individuals just carry one CFTR mutation and have thus one normal CFTR gene (typical example: parents of patients with cystic fibrosis) . The amount of normal CFTR made from their CFTR genes will thus be only half of what others make; but that is certainly sufficient not to cause any disease. Most likely the fact that only half of the functioning CFTR is being made carries some advantages but often that is not known. The classical example of advantage of carrier status is sickle cell anemia and malaria.

Sickle cell anemia is caused by mutations in both copies of a specific gene and leads to disease. Here also people who just have one mutation have no disease. But these individuals have the advantage of being more resistant to malaria. In developing countries malaria is often -especially if left untreated - a fatal disease. So we have a situation where mutation in one gene in an individual will protect him from getting malaria (and prevent him from dying from it) whereas mutations in both genes cause a lethal disease. The balance between these two facts is the cause that this mutant gene continues to exist in the population. There have been hypotheses that CF carriers are more resistant to cholera. Cholera is associated with diarrhea and loss of lots of fluid. The CFTR protein is a salt channel but the activity of the channel results in secretion of water to the outside. In CF carriers the amount of water secreted will thus be lower. When CF carriers get infected with cholera, one assumed that they had less water loss and would be better protected against cholera disease. This hypothesis however did not stand the test of time since cholera was not limited to whites but occurred a lot in India. One should thus expect many CF carriers in India and this is not the case. There has to our knowledge never been a hypothesis on CF carriers and the plague.
K. De Boeck, H. Cuppens

16.02.2009