Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. Cobat, A., Gallant, C. J., Simkin, L., Black, G. F., Stanley, K., Hughes, J., Doherty, T. M., Hanekom, W. A., Eley, B., Jaïs, J., Boland-Auge, A., van Helden, P., Casanova, J., Abel, L., Hoal, E. G., Schurr, E., & Alcaïs, A. The Journal of Experimental Medicine, 206(12):2583–2591, November, 2009. 00063 doi abstract bibtex 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 \textless 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).
@article{cobat_two_2009,
title = {Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis},
volume = {206},
issn = {1540-9538},
doi = {10.1084/jem.20090892},
abstract = {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 {\textless} 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).},
language = {eng},
number = {12},
journal = {The Journal of Experimental Medicine},
author = {Cobat, Aurelie and Gallant, Caroline J. and Simkin, Leah and Black, Gillian F. and Stanley, Kim and Hughes, Jane and Doherty, T. Mark and Hanekom, Willem A. and Eley, Brian and Jaïs, Jean-Philippe and Boland-Auge, Anne and van Helden, Paul and Casanova, Jean-Laurent and Abel, Laurent and Hoal, Eileen G. and Schurr, Erwin and Alcaïs, Alexandre},
month = nov,
year = {2009},
pmid = {19901083},
pmcid = {PMC2806605},
note = {00063 },
keywords = {Chromosome Mapping, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 5, Dopamine Plasma Membrane Transport Proteins, Endemic Diseases, Female, Humans, Hypersensitivity, Delayed, Male, Mycobacterium tuberculosis, Quantitative Trait Loci, Siblings, South Africa, Tuberculin, Tuberculin Test, Tuberculosis},
pages = {2583--2591},
}
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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 \\textless 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. 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