Early Progression to Active TB Is Associated with Highly Heritable Variant in Gene Related to Monocyte Function in Infected Peruvian Populations

While the vast majority of the 1.8 billion people infected with the TB bacterium never experience active disease, an estimated 5 to 15 percent do develop full-blown infections--roughly half of them within 18 months of exposure. Why do some people develop overt disease soon after infection, while others harbor silent infections for decades and remain apparently healthy? It's a question that has continued to mystify microbiologists, infectious disease specialists, and public health experts on the forefront of the fight against TB, which continues to claim more lives globally than any other infectious pathogen. Now, a study by scientists from Harvard Medical School, Brigham and Women's Hospital, the Broad Institute of MIT and Harvard, Socios en Salud in Peru, and other institutions offers an answer: some of the risk for early disease progression is driven by several gene variants, at least one of which controls key immune functions. The research, published online on August 21, 2019 in Nature Communications, is believed to be the first large-scale study to explore the genetic underpinnings of early TB progression among people living in the same households with confirmed active and latent infections. This was a particular strength of the study, the research team said, because it ensured a meaningful and direct comparison allowing scientists to distinguish between infected progressors and infected non-progressors. The open-acess article is titled “Early Progression to Active Tuberculosis Is a Highly Heritable Trait Driven by 3q23 In Peruvians.” To be sure, researchers added, this is not the whole story, and more genes will likely be uncovered as drivers of early disease progression.
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