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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
Mycobacterium 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.
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
ISSN: 14664879
DOI: 10.1038/gene.2011.83
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