bvsalud.ris

TY  - JOUR
AU  - Lee JC
AU  - Espéli M
AU  - Anderson CA
AU  - Linterman MA
AU  - Pocock JM
AU  - Williams NJ
AU  - Roberts R
AU  - Viatte S
AU  - Fu B
AU  - Peshu N
AU  - Hien TT
AU  - Phu NH
AU  - Wesley E
AU  - Edwards C
AU  - Ahmad T
AU  - Mansfield JC
AU  - Gearry R
AU  - Dunstan S
AU  - Williams TN
AU  - Barton A
AU  - Vinuesa CG
AU  - Parkes M
AU  - Lyons PA
AU  - Smith KG
T1  - Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway.
JO  - Cell
VL  - 155 
IS  - 1
DB  - MEDLINE
DP  - http://pesquisa.bvsalud.org/
ID  - 24035192
LA  - en
SP  - 57
EP  - 69
DA  - 2013/09PY  - 2013
KW  - Artrite Reumatoide/genética
KW  - Doença de Crohn/genética
KW  - Fatores de Transcrição Forkhead/genética
KW  - Malária Falciparum/genética
KW  - Polimorfismo de Nucleotídeo Único
KW  - Animais
KW  - Artrite Reumatoide/fisiopatologia
KW  - Núcleo Celular/metabolismo
KW  - Doença de Crohn/fisiopatologia
KW  - Proteínas da Matriz Extracelular/imunologia
KW  - Fatores de Transcrição Forkhead/metabolismo
KW  - Variação Genética
KW  - Humanos
KW  - Inflamação/genética
KW  - Malária Falciparum/fisiopatologia
KW  - Camundongos
KW  - Monócitos/imunologia
KW  - Transcrição Genética
KW  - Fator de Crescimento Transformador beta/imunologia
N2  - 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 TGFß1 reduces production of proinflammatory cytokines, including TNFα, 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.
UR  - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790457/?tool=pubmed
UR  - http://dx.doi.org/10.1016/j.cell.2013.08.034
ER  -