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Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: evidence for coevolution?

McHenry, Michael L. and Bartlett, Jacquelaine and Igo, Robert P. and Wampande, Eddie M. and Benchek, Penelope and Mayanja-Kizza, Harriet and Fluegge, Kyle and Hall, Noemi B. and Gagneux, Sebastien and Tishkoff, Sarah A. and Wejse, Christian and Sirugo, Giorgio and Boom, W. Henry and Joloba, Moses and Williams, Scott M. and Stein, Catherine M.. (2020) Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: evidence for coevolution? PLoS genetics, 16 (4). e1008728.

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Official URL: https://edoc.unibas.ch/76579/

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Abstract

Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which there were 3 MTB lineages of which L4-Ugandan (L4.6) is the most recent. TB severity, measured using the Bandim TBscore, was modeled as a function of host SNP genotype, MTB lineage, and their interaction, within two independent cohorts of TB cases, N = 113 and 121. No association was found between lineage and severity, but association between multiple polymorphisms in IL12B and TBscore was replicated in two independent cohorts (most significant rs3212227, combined p = 0.0006), supporting previous associations of IL12B with TB susceptibility. We also observed significant interaction between a single nucleotide polymorphism (SNP) in SLC11A1 and the L4-Ugandan lineage in both cohorts (rs17235409, meta p = 0.0002). Interestingly, the presence of the L4-Uganda lineage in the presence of the ancestral human allele associated with more severe disease. These findings demonstrate that IL12B is associated with severity of TB in addition to susceptibility, and that the association between TB severity and human genetics can be due to an interaction between genes in the two species, consistent with host-pathogen coevolution in TB.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1553-7390
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 May 2020 14:45
Deposited On:13 May 2020 14:45

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