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https://doi.org/10.1038/gene.2011.83
Title: | Epiregulin (EREG) variation is associated with susceptibility to tuberculosis | Authors: | Thuong, N.T.T. Hawn, T.R. Chau, T.T.H. Bang, N.D. Yen, N.T.B. Thwaites, G.E. Teo, Y.Y. Seielstad, M. Hibberd, M. Lan, N.T.N. Caws, M. Farrar, J.J. Dunstan, S.J. |
Keywords: | genetic association macrophage Mycobacterium tuberculosis SNP TB tuberculosis |
Issue Date: | Apr-2012 | Citation: | Thuong, N.T.T., Hawn, T.R., Chau, T.T.H., Bang, N.D., Yen, N.T.B., Thwaites, G.E., Teo, Y.Y., Seielstad, M., Hibberd, M., Lan, N.T.N., Caws, M., Farrar, J.J., Dunstan, S.J. (2012-04). Epiregulin (EREG) variation is associated with susceptibility to tuberculosis. Genes and Immunity 13 (3) : 275-281. ScholarBank@NUS Repository. https://doi.org/10.1038/gene.2011.83 | Abstract: | Although host genetics influences susceptibility to Mycobacterium tuberculosis, the human genes regulating pathogenesis remain largely unknown. We used M. tuberculosis-stimulated macrophage gene expression profiling in conjunction with a case-control genetic association study to discover epiregulin (EREG), as a novel candidate tuberculosis (TB) susceptibility gene. Using a genome-wide association study dataset, we found that among the 21 genes with greater than 50-fold induction, EREG had the most polymorphisms associated with TB. We genotyped haplotype-tagging polymorphisms in discovery (N=337 cases, N=380 controls) and validation (N=332 cases) datasets and an EREG polymorphism (rs7675690) was associated with susceptibility to TB (genotypic comparison; corrected P=0.00007). rs7675690 was also associated more strongly with infections caused by the Beijing lineage of M. tuberculosis when compared with non-Beijing strains (controls vs Beijing, OR 7.81, P=8.7 × 10 -5; non-Beijing, OR 3.13, P=0.074). Furthermore, EREG expression was induced in monocytes and peripheral blood mononuclear cells stimulated with M. tuberculosis as well as TLR4 and TLR2/1/6 ligands. In murine macrophages, EREG expression induced by M. tuberculosis was MYD88- and TLR2-dependent. Together, these data provide the first evidence for an important role for EREG as a susceptibility gene for human TB. © 2012 Macmillan Publishers Limited All rights reserved. | Source Title: | Genes and Immunity | URI: | http://scholarbank.nus.edu.sg/handle/10635/108747 | ISSN: | 14664879 | DOI: | 10.1038/gene.2011.83 |
Appears in Collections: | Staff Publications |
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