Medrano, Luz MaríaTaxonera, CarlosGonzález-Artacho, CristinaPascual, VirginiaGómez-García, MaríaBarreiro-de Acosta, ManuelPérez-Calle, José LBermejo, FernandoLópez-Sanromán, AntonioMartín Arranz, DoloresGisbert, Javier PMendoza, Juan LuisMartín, JavierNúñez, ConcepciónUrcelay, Elena2015-10-272015-10-272015Medrano 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.; 2015:3182070962-9351http://hdl.handle.net/10668/2041Journal Article; Research Support, Non-U.S. Gov't;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.enAnticuerpos monoclonalesMarcadores biológicosEnfermedad de CrohnGenotipoHaplotiposHumanosÍleonColonInterleucina-11Polimorfismo genéticoFactor de necrosis tumoral alfaMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, MonoclonalMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn DiseaseMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::HaplotypesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine, Small::IleumMedical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Intestines::Intestine, Large::ColonMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-11Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, GeneticMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alphaResponse to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile.research article26339133open access10.1155/2015/3182071466-1861PMC4539178