title: Polymorphisms in the Pattern Recognition Receptor Mincle Gene (CLEC4E) and Association with Tuberculosis.
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.
authors.affiliation: 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.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bowker
authors.affiliation: 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.
authors.forename: Muneeb
authors.initials: M
authors.lastname: Salie
authors.affiliation: 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.
authors.forename: Haiko
authors.initials: H
authors.lastname: Schurz
authors.affiliation: 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.
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.affiliation: 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.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Kinnear
authors.affiliation: 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.
authors.forename: Eileen G
authors.initials: EG
authors.lastname: Hoal
authors.affiliation: 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. marlom@sun.ac.za.
authors.forename: Marlo
authors.initials: M
authors.lastname: Möller
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003311:Cord Factors / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C482593:CLEC4D protein, human; D003311:Cord Factors; D037181:Lectins, C-Type; D011971:Receptors, Immunologic
keywords: CLEC4E; Mincle; Mycobacterium tuberculosis; Polymorphism; Susceptibility