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Thread: Heritability of TB progression

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    Heritability of TB progression

    TB hardly enters our consciousness nowadays, but even 100 years ago it was a plague in Europe, with 1/4 of people dying of it, and many more in certain areas. Given that, I'm surprised at the 15% figure used in the study. Perhaps the poor nutrition and overcrowding, as well as lack of pasteurization increased the numbers.

    What people don't realize is that during WWII and the aftermath, almost everyone was exposed to it. Both my parents came out positive for exposure. Luckily neither came down with it.

    Yang Luo et al

    "Progression of recent Mycobacterium tuberculosis exposure to active tuberculosis is a highly heritable complex trait driven by 3q23 in Peruvians"

    Among 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% are expected to develop active tuberculosis (TB). Approximately half of these will progress to active TB within the first 18 months after infection, presumably because they fail to mount the initial immune response that contains the local bacterial spread. The other half will reactivate their latent infection later in life, likely triggered by a loss of immune competence due to factors such as HIV-associated immunosuppression or ageing. This natural history suggests that undiscovered host genetic factors may control early progression to active TB. Here, we report results from a large genome-wide genetic study of early TB progression. We genotyped a total of 4,002 active TB cases and their household contacts in Peru and quantified genetic heritability (hg2) of early TB progression to be 21.2% under the liability scale. Compared to the reported hg2 of genome-wide TB susceptibility (15.5%), this result indicates early TB progression has a stronger genetic basis than population-wide TB susceptibility. We identified a novel association between early TB progression and variants located in an enhancer region on chromosome 3q23 (rs73226617, OR=1.19; P<5×10-8). We used in silico and in vitro analyses to identify likely functional variants and target genes, highlighting new candidate mechanisms of host response in early TB progression."

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    The genus Mycobacterium generally have special properties that allow them to evade being destroyed by the immune system. For instance, Mycobacterium tuberculosis can prevent fusion of the phagosome (vesicle in which it was eaten) with lysosomes (vesicles with hydrolytic enzymes), and thus can survive in macrophages indefinitely. Belonging to this same genus is a bacteria that causes leprosy. The body really does not have a good way of fighting these infections, except for walling them off in granulomas. This is why people with compromised immune systems have these reactivations. After all, the number one cause of death in AIDS patients is tuberculosis. The treatment for these infections includes an extensive regimen of several antibiotics, and you can see then how demographics may play a big role in treatment.

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