People may have evolved to fight cholera

Some people in Bangladesh carry genetic alterations that seem to protect against cholera, a study shows. These changes apparently occurred over thousands of years as exposure to the disease exerted a form of natural selection on people in the Ganges River Delta.

Although cholera can cause lethal, dehydrating diarrhea, 60 to 90 percent of people infected with it experience few or no symptoms. That often happens when people have had prior exposure to the microbe that causes the disease, says Glenn Morris, an infectious disease physician at the University of Florida in Gainesville. But a portion of that protection may reflect underlying genetic differences in susceptibility to cholera, he says, and a possible biological mechanism for such safeguards.

Previous research had found a possible adaptation response to cholera in the Ganges Delta, which includes parts of Bangladesh. For reasons that are still unclear, people with type O blood are more susceptible to cholera than people in other blood groups. Perhaps not coincidentally, the Ganges Delta has the lowest occurrence of type O blood in the world, says Regina LaRocque, an infectious disease physician at Harvard Medical School and Massachusetts General Hospital in Boston.

But aside from blood type, LaRocque and others couldn’t explain why some families seem less susceptible to cholera than others. In the new study, she and her colleagues identified genetic variants in families from Dhaka, Bangladesh, that stood apart from variants in people from East Asia, West Africa or Europe.

The researchers then tested the DNA of 105 cholera patients in Dhaka and 167 people who shared households with them but who didn’t have the disease. When they looked closely at 28 of the highlighted genetic variants, there were five genes that differed between the people who were sick and those who weren’t, the researchers report in the July 3 Science Translational Medicine. 

Some of the genes are implicated in inflammation, which runs amok in the intestines in response to the cholera toxin. But LaRocque says none of the genes make proteins that directly control inflammation. Rather, they are components that modulate or tweak that response, she says. That makes sense, she says, since entirely shutting down an immune response such as inflammation could leave a person vulnerable to other pathogens.

In a separate analysis, the scientists looked at patients who had severe cholera. This group was more likely than people impervious to cholera to have three other genetic variants, all of which are implicated in regulating fluid loss from the intestines.

Understanding the clues provided by these differences in immune responses to cholera might someday enable scientists to induce a kind of long-lasting protection that rivals what people garner after a bout with the disease itself, says study coauthor Elinor Karlsson, a Harvard geneticist and coauthor of the study. The need is great because the current cholera vaccine doesn’t provide long-lasting protection.