Re: Is there a connection between cystic fibrosis and cholera?

Dear Josh,

To answer your question, yes, there is thought to be a connection between 
cholera and cystic fibrosis.  Before we go on let me review a few important 
points about each cholera and cystic fibrosis. 
 
Cystic fibrosis (CF) is the most common fatal genetic disease among white 
Americans.  CF is a problem caused by a mutation in a gene for a chloride 
channel called CFTR (cystic fibrosis transmembrane regulator).  A mutation 
in both of the CFTR genes (everyone has two copies of each gene) results in 
the clinical disease known as cystic fibrosis.   The result is very thick 
secretions especially in the lungs, resulting in pneumonia, and in the 
pancreas, resulting in diabetes and malabsorption (unable to digest food). 
 Even though the main problems in cystic fibrosis patients are with the 
lungs and pancreas, the defective ion channel is in cells all over the 
body, which is where cholera comes in...

A bacteria called Vibrio cholera secretes a toxin that binds to the CFTR 
channel, causing it to turn on and secrete chloride into the intestine.  
Water then follws the chloride out of the cells (diffusion), and also water 
cannot be absorbed from the intestine into the cells because of all the 
ions inside the intestine. The result is up to 1 liter of watery diarrhea 
per hour, which can lead very quickly to death if oral rehydration therapy 
is not begun quickly.  Historically, cholera has killed a great many 
people.  

Here is where the two diseases come together:  if the CFTR channel has a 
defect because of a mutation in its gene, the cholera toxin cannot bind to 
the channel.  Having a mutation in your CFTR is only beneficial, however, 
if you only have one mutated gene (heterozygous).  Then you are protected 
from a very serious case of cholera, and instead will have a milder case.  
If both of your CFTR genes are mutated (homozygous), then you will have a 
very serious case of cystic fibrosis.  Historically, people with CF died as 
children, so this protection against cholera was insignificant for a person 
homozygous for the mutated gene, but very significant for the heterozygous 
person.

Many scientists believe that cholera epidemics have selected for those with 
one CFTR mutation.  In other words, because the mutation gives an advantage 
 to those who have it, they lived while other people died, so the mutated 
gene continued to be passed along.  There are three pieces of evidence that 
support this theory: 1) there are many different defects in the CFTR gene  
2) the mutated gene has a very high frequency in the population 3) and the 
very old age of the mutation (scientists estimate that it is 50,000 years 
old) (Bertrandpetit, J. "Ciba Found Symp." 1996. v. 197.p.97-114).  These 
points all support the theory that cholera has selected for a mutated CFTR, 
because if these mutations were only harmful and not helpful, so many 
different mutations would not exist in the same ion channel for so many 
years in so many different people.

Thank you for your question,

Sarah Martin Mason, Mad Scientist, Tulane University School of Medicine