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Polymorphisms in the Pattern Recognition Receptor Mincle Gene (CLEC4E) and Association with Tuberculosis

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Abstract

The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6′,6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages. Mincle is encoded by CLEC4E, and we investigated polymorphisms in this gene to assess its role in tuberculosis susceptibility. Four tagging single nucleotide polymorphisms (SNPs) (rs10841845, rs10841847, rs10841856 and rs4620776) were genotyped using TaqMan® SNP assays in 416 tuberculosis cases and 405 healthy controls. Logistic regression models were used for analysis. No association was detected with any of the SNPs analysed. This research highlights tuberculosis disease complexity where recognition proteins which specifically bind mycobacterial glycolipids cannot be conclusively associated with the disease in genetic studies.

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Acknowledgments

We thank all participants for their collaboration. We thank Michelle Daya for providing analysis scripts. The funding sources had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

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Authors and Affiliations

  1. SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Teaching Building, 4th Floor, Room 4036, Tygerberg, Cape Town, 7505, South Africa

    Nicholas Bowker, Muneeb Salie, Haiko Schurz, Paul D. van Helden, Craig J. Kinnear, Eileen G. Hoal & Marlo Möller

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  1. Nicholas Bowker
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  2. Muneeb Salie
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  3. Haiko Schurz
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  4. Paul D. van Helden
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  5. Craig J. Kinnear
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  6. Eileen G. Hoal
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Correspondence to Marlo Möller.

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Bowker, N., Salie, M., Schurz, H. et al. Polymorphisms in the Pattern Recognition Receptor Mincle Gene (CLEC4E) and Association with Tuberculosis. Lung 194, 763–767 (2016). https://doi.org/10.1007/s00408-016-9915-y

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  • DOI: https://doi.org/10.1007/s00408-016-9915-y

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