Hum Immunol. 2014 Jan;75(1):71-5.

Role of TNFRSF1B polymorphisms in the response of Crohn’s disease patients to infliximab.

  • 1Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
  • 2Gastroenterology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
  • 3Institute of Parasitology and Biomedicine, CSIC, Granada, Spain.
  • 4Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Spain.
  • 5Department of Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain.
  • 6Department of Gastroenterology, Hospital Alcorcón, Madrid, Spain.
  • 7Department of Gastroenterology, Hospital Fuenlabrada, Madrid, Spain.
  • 8Department of Gastroenterology, Hospital Ramón y Cajal, Madrid, Spain.
  • 9Department of Gastroenterology, Hospital La Paz, Madrid, Spain.
  • 10Department 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.
  • 11Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Electronic address: conchita.npardo@gmail.com.

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.

PMID: 24121042
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