Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile
| Autor: | Carlos Taxonera, Dolores Martín Arranz, Juan Luis Mendoza, José Lázaro Pérez-Calle, Fernando Bermejo, Concepción Núñez, Virginia Pascual, Javier P. Gisbert, María Gómez-García, Elena Urcelay, Javier Martín, Cristina González-Artacho, Luz Maria Medrano, Antonio López-Sanromán, Manuel Barreiro-de Acosta |
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| Přispěvatelé: | [Medrano,LM, Pascual,V, Núñez,C, Urcelay,E] Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Taxonera,C, Mendoza,JL] Gastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [González-Artacho,C, Gómez-García,M] Gastroenterology Department, Virgen de las Nieves Hospital, Granada, Spain. [Barreiro-de Acosta,M] Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. [Perez-Calle,JL] Gastroenterology Department, Alcorcón Hospital, Madrid, Spain. [Bermejo,F] Gastroenterology Department, Fuenlabrada Hospital, Madrid, Spain. [López-Sanromán,A] Gastroenterology Department, Fuenlabrada Hospital, Madrid, Spain. [Martín Arranz,D] Gastroenterology Department, La Paz Hospital, Madrid, Spain. [Gisber,JP] Gastroenterology Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. [Martín,J] Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla, Granada, Spain., Financial support for the study was provided by Fundación Mutua Madrileña. |
| Rok vydání: | 2015 |
| Předmět: |
Male
Polimorfismo genético Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine Large::Colon [Medical Subject Headings] Cell Cycle Proteins Disease Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine Small::Ileum [Medical Subject Headings] Genetic analysis Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Crohn Disease Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha [Medical Subject Headings] Genotype Young adult Crohn's disease Marcadores biológicos Interleukin-11 Humanos Antirheumatic Agents Female Haplotipos Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] Interleucina-11 lcsh:RB1-214 medicine.drug Adult Article Subject Adolescent Colon Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-11 [Medical Subject Headings] Immunology Biology Young Adult Íleon Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] lcsh:Pathology medicine Calgranulin B Humans Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies Monoclonal [Medical Subject Headings] Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease [Medical Subject Headings] Calgranulin A Enfermedad de Crohn Genotyping Haplotype Cell Biology Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic [Medical Subject Headings] medicine.disease Infliximab Factor de necrosis tumoral alfa Anticuerpos monoclonales Clinical Study Genotipo Cell Adhesion Molecules |
| Zdroj: | Mediators of Inflammation Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Mediators of Inflammation, Vol 2015 (2015) |
| ISSN: | 1466-1861 0962-9351 |
| DOI: | 10.1155/2015/318207 |
| Popis: | 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, andIL11) 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); andIL11(rs1126760*C/rs1042506*G;P=0.07). These differences were amplified in patients with colonic and ileocolonic location for all but theTNFAIP6haplotype, 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. |
| Databáze: | OpenAIRE |
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