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Tuberculosis resistance

Gene ExpressionBy Razib KhanDecember 7, 2009 3:46 PM


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Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis:

Approximately 20% of persons living in areas hyperendemic for tuberculosis (TB) display persistent lack of tuberculin skin test (TST) reactivity and appear to be naturally resistant to infection by Mycobacterium tuberculosis. Among those with a positive response, the intensity of TST reactivity varies greatly. The genetic basis of TST reactivity is not known. We report on a genome-wide linkage search for loci that have an impact on TST reactivity, which is defined either as zero versus nonzero (TST-BINa) or as extent of TST in millimeters (TST-quantitative trait locus [QTL]) in a panel of 128 families, including 350 siblings, from an area of South Africa hyperendemic for TB. We detected a major locus (TST1) on chromosomal region 11p14 (P = 1.4 x 10-5), which controls TST-BINa, with a lack of responsiveness indicating T cell-independent resistance to M. tuberculosis. We also detected a second major locus (TST2) on chromosomal region 5p15 (P < 10-5), which controls TST-QTL or the intensity of T cell-mediated delayed type hypersensitivity (DTH) to tuberculin. Fine mapping of this region identified SLC6A3, encoding the dopamine transporter DAT1, as a promising gene for further studies. Our results pave the way for the understanding of the molecular mechanisms involved in resistance to M. tuberculosis infection in endemic areas (TST1) and for the identification of critical regulators of T cell-dependent DTH to tuberculin (TST2).

They focus on rs250682 in particular. It seems to me that personal genomics in the interests of health has been a little over-hyped, but I will be happy when people with allergies can get their genes sequenced rather than taking these irritating skin tests. Citation: Aurelie Cobat, Caroline J. Gallant, Leah Simkin, Gillian F. Black, Kim Stanley, Jane Hughes, T. Mark Doherty, Willem A. Hanekom, Brian Eley, Jean-Philippe Jaïs, Anne Boland-Auge, Paul van Helden, Jean-Laurent Casanova, Laurent Abel, Eileen G. Hoal, Erwin Schurr, and Alexandre Alcaïs, Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis, J. Exp. Med., Nov 2009; 206: 2583 - 2591.

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