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Mediators of Inflammation
Volume 2015, Article ID 318207, 8 pages
http://dx.doi.org/10.1155/2015/318207
Clinical Study

Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile

1Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
2Gastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
3Gastroenterology Department, Virgen de las Nieves Hospital, 18014 Granada, Spain
4Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain
5Gastroenterology Department, Alcorcón Hospital, 28922 Madrid, Spain
6Gastroenterology Department, Fuenlabrada Hospital, 28942 Madrid, Spain
7Gastroenterology Department, Ramón y Cajal Hospital, 28034 Madrid, Spain
8Gastroenterology Department, La Paz Hospital, 28046 Madrid, Spain
9Gastroenterology Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IP), 28006 Madrid, Spain
10Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28002 Madrid, Spain
11Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla, 18100 Granada, Spain

Received 16 December 2014; Revised 11 March 2015; Accepted 11 March 2015

Academic Editor: Peter Szodoray

Copyright © 2015 Luz María Medrano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (rs11205276G/rs3014866C/rs724781C/rs3006488A; ); G0S2 (rs4844486A/rs1473683T; ); TNFAIP6 (rs11677200C/rs2342910A/rs3755480G/rs10432475A; ); and IL11 (rs1126760C/rs1042506G; ). 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.