title: Role of TNFRSF1B polymorphisms in the response of Crohn's disease patients to infliximab.
abstract: Infliximab (IFX) is a valid treatment for Crohn's disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A (TNFRSF1A) and 1B (TNFRSF1B) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B. Comparisons between groups were performed with chi-square tests or the Fisher's exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p = 0.015, OR = 1.78, 95% CI 1.09-2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p = 0.033 vs nonresponders and p = 0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients.
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Medrano
authors.affiliation: Gastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Taxonera
authors.affiliation: Institute of Parasitology and Biomedicine, CSIC, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Márquez
authors.affiliation: Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Barreiro-de Acosta
authors.affiliation: Department of Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-García
authors.affiliation: Department of Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: C
authors.initials: C
authors.lastname: González-Artacho
authors.affiliation: Department of Gastroenterology, Hospital Alcorcón, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Pérez-Calle
authors.affiliation: Department of Gastroenterology, Hospital Fuenlabrada, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Bermejo
authors.affiliation: Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Sanromán
authors.affiliation: Department of Gastroenterology, Hospital La Paz, Madrid, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Martín Arranz
authors.affiliation: Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHED), Madrid, Spain.
authors.forename: J P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Gastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Mendoza
authors.affiliation: Institute of Parasitology and Biomedicine, CSIC, Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martín
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Urcelay
authors.affiliation: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Electronic address: conchita.npardo@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Núñez
mesh_terms: D000328:Adult; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D000069285:Infliximab