ArticlePLoS genetics2017
A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.Genome medicine · 2025Article
- Noncanonical T cell responses are associated with protection from tuberculosis in mice and humans.The Journal of experimental medicine · 2025Article
- New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.Cellular & molecular immunology · 2023Review
- Genetic epidemiology of resistance to M. tuberculosis Infection: importance of study design and recent findings.Genes and immunity · 2023Review
- Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA.Human molecular genetics · 2023Article
- Th2 Cytokines (Interleukin-5 and -9) Polymorphism Affects the Response to Anti-TNF Treatment in Polish Patients with Ankylosing Spondylitis.International journal of molecular sciences · 2022Article
- REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations.PLoS genetics · 2021Article
- Host genetics and infectious disease: new tools, insights and translational opportunities.Nature reviews. Genetics · 2021Review
- Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes.International journal of molecular sciences · 2020Review
- Observational
- Fine-mapping analysis of a chromosome 2 region linked to resistance to Mycobacterium tuberculosis infection in Uganda reveals potential regulatory variants.Genes and immunity · 2019Article
- Long-term Stability of Resistance to Latent Mycobacterium tuberculosis Infection in Highly Exposed Tuberculosis Household Contacts in Kampala, Uganda.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Advances in the understanding of Mycobacterium tuberculosis transmission in HIV-endemic settings.The Lancet. Infectious diseases · 2019Review
- Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection.Nature reviews. Immunology · 2018Review
- Genetic Resistance toFrontiers in immunology · 2018Review
- Neutrophils: Innate Effectors of TB Resistance?Frontiers in immunology · 2018Review
- Early clearance versus control: what is the meaning of a negative tuberculin skin test or interferon-gamma release assay following exposure toF1000Research · 2018Review
- Genomics of human pulmonary tuberculosis: from genes to pathways.Current genetic medicine reports · 2017Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
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.
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Registered trials
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