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

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• 作者：Nicholas Bowker ; Muneeb Salie ; Haiko Schurz ; Paul D. van Helden ; Craig J. Kinnear…
• 关键词：CLEC4E ; Mincle ; Susceptibility ; Polymorphism ; Mycobacterium tuberculosis
• 刊名：Lung
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：194
• 期：5
• 页码：763-767
• 全文大小：363 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pneumology and Respiratory System
  
• 出版者：Springer New York
• ISSN：1432-1750
• 卷排序：194

文摘

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.