Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile
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) rep...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/318207 |
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| author | Luz María Medrano Carlos Taxonera Cristina González-Artacho Virginia Pascual María Gómez-García Manuel Barreiro-de Acosta José L. Pérez-Calle Fernando Bermejo Antonio López-Sanromán Dolores Martín Arranz Javier P. Gisbert Juan Luis Mendoza Javier Martín Concepción Núñez Elena Urcelay |
| author_facet | Luz María Medrano Carlos Taxonera Cristina González-Artacho Virginia Pascual María Gómez-García Manuel Barreiro-de Acosta José L. Pérez-Calle Fernando Bermejo Antonio López-Sanromán Dolores Martín Arranz Javier P. Gisbert Juan Luis Mendoza Javier Martín Concepción Núñez Elena Urcelay |
| author_sort | Luz María Medrano |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-07476914c5ab40dea276468738fd28da |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-07476914c5ab40dea276468738fd28da2025-02-03T05:45:15ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/318207318207Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression ProfileLuz María Medrano0Carlos Taxonera1Cristina González-Artacho2Virginia Pascual3María Gómez-García4Manuel Barreiro-de Acosta5José L. Pérez-Calle6Fernando Bermejo7Antonio López-Sanromán8Dolores Martín Arranz9Javier P. Gisbert10Juan Luis Mendoza11Javier Martín12Concepción Núñez13Elena Urcelay14Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainGastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainGastroenterology Department, Virgen de las Nieves Hospital, 18014 Granada, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainGastroenterology Department, Virgen de las Nieves Hospital, 18014 Granada, SpainGastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, SpainGastroenterology Department, Alcorcón Hospital, 28922 Madrid, SpainGastroenterology Department, Fuenlabrada Hospital, 28942 Madrid, SpainGastroenterology Department, Ramón y Cajal Hospital, 28034 Madrid, SpainGastroenterology Department, La Paz Hospital, 28046 Madrid, SpainGastroenterology Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IP), 28006 Madrid, SpainGastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainInstituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla, 18100 Granada, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainImmunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainSubstantial 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.http://dx.doi.org/10.1155/2015/318207 |
| spellingShingle | Luz María Medrano Carlos Taxonera Cristina González-Artacho Virginia Pascual María Gómez-García Manuel Barreiro-de Acosta José L. Pérez-Calle Fernando Bermejo Antonio López-Sanromán Dolores Martín Arranz Javier P. Gisbert Juan Luis Mendoza Javier Martín Concepción Núñez Elena Urcelay Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile Mediators of Inflammation |
| title | Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile |
| title_full | Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile |
| title_fullStr | Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile |
| title_full_unstemmed | Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile |
| title_short | Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile |
| title_sort | response to infliximab in crohn s disease genetic analysis supporting expression profile |
| url | http://dx.doi.org/10.1155/2015/318207 |
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