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A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

Genes & Immunity volume 14, pages 420–426 (2013)Cite this article

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Abstract

Legionella pneumophila (Lp), the etiologic agent of Legionnaires’ disease (LD), is an important cause of community-acquired and nosocomial pneumonia. However, the host immune and genetic determinants of human susceptibility to Lp are poorly understood. Here we show that both TLR6 and TLR1 cooperate with TLR2 to recognize Lp in transfected HEK293 cells. We also perform a human genetic association study of 14 candidate single-nucleotide polymorphisms in Toll-like receptors (TLRs) 1, 2 and 6 in 98 LD cases and 268 controls from the Netherlands. No polymorphisms in TLR1 or TLR2 were associated with LD. A TLR6 polymorphism, 359T>C (rs5743808), was associated with an elevated risk of LD in genotypic and dominant (odds ratio (OR) 5.83, P=7.9 × 10−5) models. The increased risk in persons with 359 TC or CC genotypes was further enhanced among smokers. In a multivariate model, 359T>C was associated with a higher risk of LD (OR 4.24, P=0.04), than any other variable, including age and smoking. Together, these data suggest that the human TLR6 variant, 359T>C, is an independent risk factor for LD.

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Acknowledgements

We thank Kamilla D Lettinga for establishing the database for patients and HC Boshuizen for establishing the database for controls. We thank Drs Alan Aderem of Seattle BioMed and Marta Janer formerly of Institute for Systems Biology for advice and genotyping assistance and Sarah Li, Rick Wells and Malinka Jansson-Hutson for technical assistance.

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Authors and Affiliations

  1. Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA

    E A Misch, S J Skerrett & T R Hawn

  2. Department of Internal Medicine, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands

    A Verbon

  3. Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    J M Prins

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  1. E A Misch
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Correspondence to E A Misch.

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Misch, E., Verbon, A., Prins, J. et al. A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease. Genes Immun 14, 420–426 (2013). https://doi.org/10.1038/gene.2013.34

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