RT Journal Article
T1 Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile.
A1 Medrano, Luz María
A1 Taxonera, Carlos
A1 González-Artacho, Cristina
A1 Pascual, Virginia
A1 Gómez-García, María
A1 Barreiro-de Acosta, Manuel
A1 Pérez-Calle, José L
A1 Bermejo, Fernando
A1 López-Sanromán, Antonio
A1 Martín Arranz, Dolores
A1 Gisbert, Javier P
A1 Mendoza, Juan Luis
A1 Martín, Javier
A1 Núñez, Concepción
A1 Urcelay, Elena
K1 Anticuerpos monoclonales
K1 Marcadores biológicos
K1 Enfermedad de Crohn
K1 Genotipo
K1 Haplotipos
K1 Humanos
K1 Íleon
K1 Colon
K1 Interleucina-11
K1 Polimorfismo genético
K1 Factor de necrosis tumoral alfa
AB Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276* G/rs3014866* C/rs724781* C/rs3006488* A; P = 0.05); G0S2 (rs4844486* A/rs1473683* T; P = 0.15); TNFAIP6 (rs11677200* C/rs2342910* A/rs3755480* G/rs10432475* A; P = 0.10); and IL11 (rs1126760* C/rs1042506* G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.
PB Hindawi Publishing Corporation
SN 0962-9351
YR 2015
FD 2015
LK http://hdl.handle.net/10668/2041
UL http://hdl.handle.net/10668/2041
LA en
NO Medrano LM, Taxonera C, González-Artacho C, Pascual V, Gómez-García M, Barreiro-de Acosta M, et al. Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile. Mediators Inflamm.; 2015:318207
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025