دورية أكاديمية
A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.
| العنوان: | A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa. |
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| المؤلفون: | Rafal S Sobota, Catherine M Stein, Nuri Kodaman, Isaac Maro, Wendy Wieland-Alter, Robert P Igo, Albert Magohe, LaShaunda L Malone, Keith Chervenak, Noemi B Hall, Mecky Matee, Harriet Mayanja-Kizza, Moses Joloba, Jason H Moore, William K Scott, Timothy Lahey, W Henry Boom, C Fordham von Reyn, Scott M Williams, Giorgio Sirugo |
| المصدر: | PLoS Genetics, Vol 13, Iss 6, p e1006710 (2017) |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | Genetics, QH426-470 |
| الوصف: | One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between a dominant model of rs877356 and binary TST status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the most significant association (p = 1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and TH2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected, HIV-positive participants with extensive exposure increases the power to detect associations in complex infectious disease. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC5495514?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1006710 |
| URL الوصول: | https://doaj.org/article/39b8f996319a481d8ac25d7c8934bd1c |
| رقم الأكسشن: | edsdoj.39b8f996319a481d8ac25d7c8934bd1c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537390 15537404 |
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| DOI: | 10.1371/journal.pgen.1006710 |