Gene Increases Risk Of Tuberculosis

Infections with Mycobacterium tuberculosis, the bacterium that causes TB, are on the rise, with an estimated eight million new infections and two million TB-induced deaths occurring annually. But not all people who are exposed to this bug become ill -- a phenomenon largely explained by genetic differences that make some individuals more prone to developing disease than others. Indeed, a recent scientific study found that a particular region on the human chromosome 17 was associated with increased risk of developing active tuberculosis, but the exact gene(s) responsible for this effect was not identified.

Flores-Villanueva and colleagues show that the culprit behind the increased susceptibility to TB was a small change in the gene that encodes a protein called MCP-1 (the MCP-1 gene resides of chromosome 17). The genetic change was a tiny one, with the DNA sequence differing by only a single nucleotide (the building blocks of DNA). This change, which resulted in increased production of the MCP-1 protein, was five times more prevalent in individuals with active TB than in those who were infected but remained healthy.

MCP-1 is a protein that helps attract immune cells to sites of infection. For this reason, this protein is important during the early immune response to TB-causing bacteria. But extremely high levels of MCP-1 can be dangerous, as they inhibit the production of another immune protein called interleukin-12. Interleukin-12 is required to activate the immune cells that fight off the infection once they arrive on the scene. In an accompanying commentary article, geneticists Alexandre Alcais, Jean-Laurent Casanova and their colleagues at the University of Paris note that this is the largest genetic impact on adult TB that has ever been described.