Tuberculosis Susceptibility Has Genetic Basis

An ancient disease, tuberculosis continues to wreak havoc around the world.

According to the World Health Report (WHO), roughly 10 million cases occurred in 2015 alone, with 1.8 million deaths. Undeniably, resource-limited nations bear the brunt of tuberculosis mortality, with the HIV epidemic contributing to the problem. Tuberculosis that is resistant to multiple drugs is also an issue. Now, researchers are gaining a greater understanding of the role that human genetics plays in determining who contracts the illness as well as how severely it impacts its victims.

The last few years have brought remarkable advancements in the ability of scientists to study the genetic basis of human susceptibility to disease. Malaria, HIV, and hepatitis C all have been found to have genetic variants that determine the precise mechanisms by which these disease pathogens operate inside a human body.

Researchers are now turning their attention to Mycobacterium tuberculosis, the bacterial species that causes tuberculosis infection. Roughly a third of the world’s individuals harbor Mycobacterium tuberculosis, with a 1 in 10 lifetime risk of developing the disease. But what determines who in this group will actually contract tuberculosis and how deadly it will be?

A group of scientists in France, Switzerland, and the United States conducted a review of various studies examining the genetic underpinnings of tuberculosis susceptibility and resistance. While they acknowledge that these studies have been challenging, researchers have been making headway. Studies of severe tuberculosis in children reveal a likely genetic cause. Various studies on twins show that identical twins are much more likely than fraternal twins to have similar experiences with tuberculosis. The report’s authors also cited studies of racially integrated nursing homes in which African-American residents were twice as likely as white residents to contract tuberculosis, suggesting an underlying genetic propensity. Animal studies, too, have helped shed light on the genes underlying tuberculosis contraction.

So far, the scientific community has identified just a handful of gene variants that correspond to tuberculosis susceptibility, although the report’s authors note that a lack of consistency and inability to replicate results have been an obstacle. More research is needed into how genes affect an individual’s response to anti-tuberculosis drugs; whether the specific dose of infection affects whether an individual will contract the illness and how severely; and how much of a role coinfections play in susceptibility to tuberculosis.

The genetic basis for human susceptibility and resistance to tuberculosis needs to be further explored in order to prevent future cases and treat existing ones, according to the report’s authors.

“Historical observations, heritability estimates, linkage analyses, and genome-wide scans indicate that human resistance to tuberculosis infection has a strong genetic basis, which is likely to be a consequence of evolutionary counter-response to microbial virulence,” they wrote in the report’s conclusion. “Mendelian studies have also provided the first evidence that severe tuberculosis in children could be due to single gene inborn errors of immunity. However, much is yet to be learned regarding susceptibility to disease, in particular, pulmonary tuberculosis, from studies of human genetic diversity and of interactions between host and pathogen genomes.”

This need is particularly acute in Africa, according to the authors, as that continent bears a disproportionate share of the world’s tuberculosis burden.

Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.