Shiloh
Editor, Senior Moderator
Source: https://www.rockefeller.edu/news/24...ation-responsible-tuberculosis-vulnerability/
Study identifies genetic mutation responsible for tuberculosis vulnerability
December 21, 2018
If you live in the United States, you are unlikely to come into contact with the microbe that causes tuberculosis. Your odds of encountering the microbe are so low, in fact, that risk factors for the disease can easily go unnoticed: If you happened to carry a gene that predisposed you to tuberculosis, you likely wouldn?t know.
New findings from Rockefeller scientists reveal that such a genetic variant indeed exists?and that it?s surprisingly common.
The researchers also uncovered genetic mutations that rob the immune system of its ability to combat more ubiquitous germs of the same bacterial family, mycobacteria. In two new studies, both published in Science Immunology, they elucidate molecular abnormalities that make people vulnerable to mycobacterial infections. This research also points to strategies for treating or preventing some cases of tuberculosis (TB).
The most common mutation you?ve never heard of
About one in five people worldwide are infected with Mycobacterium tuberculosis, the bacterium that causes TB. Of those, only 10 percent, at most, will show symptoms?because most immune systems have tools to fight the microbe. When these tools are absent or dysfunctional, however, the infection can damage the lungs and other organs, and even cause death.
Hoping to better understand why only some people are prone to TB, Jean-Laurent Casanova worked with clinicians across the world to collect DNA samples from patients with active forms of the disease. By analyzing these samples, the researchers discovered that the risk of developing TB is heightened in people who have two copies of a particular variation to the gene coding for the enzyme TYK2. Moreover, the researchers found, this genetic condition is fairly widespread.
?In Europeans, one in 600 people have two copies of this TYK2 variation. And in the rest of the population the rate is between one in 1,000 to one in 10,000?which is still not rare,? says Casanova. Putting these numbers in perspective, he adds: ?Here at Rockefeller, there are probably around four to six people who have this genetic predisposition to TB.? Yet, that is not to say that those people will actually develop the disease?and, in fact, they probably won?t.
Put simply: People don?t acquire TB if they don?t come into contact with Mycobacterium tuberculosis. And in the United States and Europe, the risk of being exposed to the microbe is very low. As a result, a New Yorker with a TYK2 mutation might never find out that she is genetically vulnerable?that is, unless she travels to a location where the microbe is rampant.
Says Casanova: ?In New York, someone can have this mutation and their risk of getting TB is effectively zero. But if that person goes to work in a TB hospital in Africa, then the likelihood of getting TB is high?one hundredfold higher than it would be for a person without the genetic variant.?
Historically, a person with a TKY2 mutation would be unaware of her susceptibility until it was too late. However, now that researchers have identified this risk factor, individuals travelling to regions where TB is common can obtain genetic tests to find out whether they are vulnerable to the disease...
Study identifies genetic mutation responsible for tuberculosis vulnerability
December 21, 2018
If you live in the United States, you are unlikely to come into contact with the microbe that causes tuberculosis. Your odds of encountering the microbe are so low, in fact, that risk factors for the disease can easily go unnoticed: If you happened to carry a gene that predisposed you to tuberculosis, you likely wouldn?t know.
New findings from Rockefeller scientists reveal that such a genetic variant indeed exists?and that it?s surprisingly common.
The researchers also uncovered genetic mutations that rob the immune system of its ability to combat more ubiquitous germs of the same bacterial family, mycobacteria. In two new studies, both published in Science Immunology, they elucidate molecular abnormalities that make people vulnerable to mycobacterial infections. This research also points to strategies for treating or preventing some cases of tuberculosis (TB).
The most common mutation you?ve never heard of
About one in five people worldwide are infected with Mycobacterium tuberculosis, the bacterium that causes TB. Of those, only 10 percent, at most, will show symptoms?because most immune systems have tools to fight the microbe. When these tools are absent or dysfunctional, however, the infection can damage the lungs and other organs, and even cause death.
Hoping to better understand why only some people are prone to TB, Jean-Laurent Casanova worked with clinicians across the world to collect DNA samples from patients with active forms of the disease. By analyzing these samples, the researchers discovered that the risk of developing TB is heightened in people who have two copies of a particular variation to the gene coding for the enzyme TYK2. Moreover, the researchers found, this genetic condition is fairly widespread.
?In Europeans, one in 600 people have two copies of this TYK2 variation. And in the rest of the population the rate is between one in 1,000 to one in 10,000?which is still not rare,? says Casanova. Putting these numbers in perspective, he adds: ?Here at Rockefeller, there are probably around four to six people who have this genetic predisposition to TB.? Yet, that is not to say that those people will actually develop the disease?and, in fact, they probably won?t.
Put simply: People don?t acquire TB if they don?t come into contact with Mycobacterium tuberculosis. And in the United States and Europe, the risk of being exposed to the microbe is very low. As a result, a New Yorker with a TYK2 mutation might never find out that she is genetically vulnerable?that is, unless she travels to a location where the microbe is rampant.
Says Casanova: ?In New York, someone can have this mutation and their risk of getting TB is effectively zero. But if that person goes to work in a TB hospital in Africa, then the likelihood of getting TB is high?one hundredfold higher than it would be for a person without the genetic variant.?
Historically, a person with a TKY2 mutation would be unaware of her susceptibility until it was too late. However, now that researchers have identified this risk factor, individuals travelling to regions where TB is common can obtain genetic tests to find out whether they are vulnerable to the disease...
