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Author (up) Medrano, L.M.; Taxonera, C.; Gonzalez-Artacho, C.; Pascual, V.; Gomez-Garcia, M.; Barreiro-de Acosta, M.; Perez-Calle, J.L.; Bermejo, F.; Lopez-Sanroman, A.; Martin Arranz, D.; Gisbert, J.P.; Mendoza, J.L.; Martin, J.; Nunez, C.; Urcelay, E. url  doi
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  Title Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile Type Journal Article
  Year 2015 Publication Mediators of Inflammation Abbreviated Journal Mediators Inflamm  
  Volume 2015 Issue Pages 318207  
  Keywords  
  Abstract 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.  
  Address Immunology Department, Hospital Clinico San Carlos, Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), 28040 Madrid, Spain  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0962-9351 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26339133 Approved no  
  Call Number ref @ user @ Serial 73726  
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