Single genetic change ‘can multiply TB risk by seven’

Mycobacterium tuberculosis colony Copyright: CDC/Dr. George Kubica

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One small genetic change can make people up to seven times more likely of developing the symptoms of tuberculosis (TB), according to a report in The Journal of Experimental Medicine next week (19 December).

The report shows how a team of Korean, Mexican and US scientists have identified a gene in which a small alteration can make Mexican patients infected with TB nearly five and a half times more likely to develop the disease.

In South Korea, the researchers found that the effect was even stronger: patients with the altered gene were up to 6.9 times more likely to display symptoms.

This is the biggest known genetic impact on adult tuberculosis; write Alexandre Alcaïs and colleagues in an accompanying article.

Only ten per cent of people infected with the TB-causing bacterium Mycobacterium tuberculosis develop the disease — a phenomenon largely put down to genetic differences between individuals.

Studies on identical and non-identical twins in the 1930s first implicated genetic factors in the disease. More recently, researchers identified one region on human chromosome 17 that appeared to influence how likely people were to develop symptoms.

Now, Pedro Flores-Villanueva of the University of Texas, United States, and his colleagues have pinpointed this increased susceptibility to a single change in a particular gene on chromosome 17.

They found that this change reduces the body’s ability to fight infection by the TB bacterium, increasing the risk that infection will lead to disease.

However, these results contradict a 2004 Brazilian study which did not find a link between the same genetic change and TB.

Flores-Villanueva and his colleagues suggest that the contradiction may result from differences in the designs of the two studies or in the genetic make-up of the populations studied.

Previous work has indicated that the influence of individual genes may vary in different populations.

The fact that this particular genetic change had a strong impact in both the Mexican and Korean populations — two very distinct ethnic groups — suggests its importance in understanding how to combat tuberculosis.

Equally important is the high frequency with which the genetic modification occurs: about 50 per cent of Mexicans carry at least one copy of the change. (They need to carry two to be five and a half times more likely to develop the disease; those who have only one copy are a little over two times more susceptible.)

The incidence of tuberculosis worldwide is on the rise. Almost nine million new cases and two million deaths occur every year.

Link to full abstract of paper by Flores-Villanueva et al.

Link to full abstract of accompanying article by Alcaïs et al.

The Journal of Experimental Medicine doi: 10.1084/jem20050126 (2005) [Flores-Villanueva et al.]
The Journal of Experimental Medicine doi: 10.1084/jem20052302 (2005) [Alcaïs et al.]