| First Author | Lee JC | Year | 2013 |
| Journal | Cell | Volume | 155 |
| Issue | 1 | Pages | 57-69 |
| PubMed ID | 24035192 | Mgi Jnum | J:346783 |
| Mgi Id | MGI:6207516 | Doi | 10.1016/j.cell.2013.08.034 |
| Citation | Lee JC, et al. (2013) Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell 155(1):57-69 |
| abstractText | The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFbeta1 reduces production of proinflammatory cytokines, including TNFalpha, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. |
