You are here
Epiregulin (EREG) variation is associated with susceptibility to tuberculosis.
Title | Epiregulin (EREG) variation is associated with susceptibility to tuberculosis. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Thuong, NTT, Hawn, TR, Chau, TTH, Bang, ND, Yen, NTB, Thwaites, GE, Teo, YY, Seielstad, M, Hibberd, M, Lan, NTN, Caws, M, Farrar, JJ, Dunstan, SJ |
Journal | Genes Immun |
Volume | 13 |
Issue | 3 |
Pagination | 275-81 |
Date Published | 2012 Apr |
ISSN | 1476-5470 |
Keywords | Alleles, Animals, Case-Control Studies, Cell Line, Epidermal Growth Factor, Genetic Predisposition to Disease, Genotype, Humans, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Polymorphism, Single Nucleotide, Tuberculosis |
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. |
DOI | 10.1038/gene.2011.83 |
Alternate Journal | Genes Immun. |
PubMed ID | 22170233 |