Susceptibility to tuberculosis is associated with TLR1 polymorphisms resulting in a lack of TLR1 cell surface expression
| Autor: | B. Schaaf, Norbert Reiling, Detlef Kirsten, Ralf René Reinert, Christoph Lange, Edmund N. L. Browne, Heidi Imhoff, Anja K. Schröder, Michael Kleines, Nicole Heussen, Adelheid Hatzmann, Hajo Haase, Adnan Al-Lahham, Peter Uciechowski, Christian Meyer, Daniela Fleischer, Lothar Rink |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Tuberculosis Genotype Immunology Single-nucleotide polymorphism Biology Ghana Polymorphism Single Nucleotide Flow cytometry Mycobacterium tuberculosis Young Adult medicine Humans Immunology and Allergy SNP Genetic Predisposition to Disease Allele Genotyping Aged Aged 80 and over Molecular Epidemiology medicine.diagnostic_test Incidence Cell Biology Middle Aged medicine.disease biology.organism_classification Toll-Like Receptor 1 Case-Control Studies Antigens Surface |
| Zdroj: | Journal of Leukocyte Biology. 90:377-388 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0409233 |
| Popis: | Human TLR1 plays an important role in host defense against Mycobacterium tuberculosis. Our aim was to analyze the association of the loss of TLR1 surface expression and TLR1 SNPs with susceptibility to TB. TLR1neg and TLR1pos cells from healthy individuals were identified by flow cytometry and compared by sequencing. TLR1 expression was measured using quantitative real-time PCR and immunoblotting. TLR1 SNP analyses of healthy individuals and TB patients from EU-C and Ghana were performed, and association of the TLR1 genotypes with increased risk of developing TB was statistically evaluated. Lack of TLR1 surface expression accompanied by impaired function was strongly associated with TLR1 SNP G743A. Genotyping of EU-C controls and TB patients revealed an association of TLR1 743A/1805G alleles [OR 2.37 (95% CI 1.13, 4.93), P=0.0219; OR 2.74 (95% CI 1.26, 6.05), P=0.0059] as well as TLR1neg 743AA/1805GG versus TLR1pos genotypes 743AG/1805TG [OR 4.98 (95% CI 1.64, 15.15), P=0.0034; OR 5.70 (95% CI 1.69, 20.35), P=0.0015] and 743AG + GG/1805TG + TT [OR 3.54 (95% CI 1.29, 9.90), P=0.0086; OR 4.17 (95% CI 1.52, 11.67), P=0.0025] with increased susceptibility to TB. No association of G743A with TB was found in Ghana as a result of a low frequency of genotype 743AA. Our data gain new insights in the role of TLR1 in M. tuberculosis defense and provide the first evidence that TLR1 variants are associated with susceptibility to TB in a low-incidence country. |
| Databáze: | OpenAIRE |
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