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Area of Science:

  • Genetics
  • Gastroenterology
  • Pharmacogenomics

Background:

  • Crohn's disease (CD) patients often show limited response to infliximab (IFX).
  • Identifying biomarkers for IFX response is crucial for clinical and economic benefits.
  • Previous studies suggested five genes (S100A8-S100A9, G0S2, TNFAIP6, IL11) are linked to IFX response based on expression profiles.

Purpose of the Study:

  • To investigate the etiological role of five specific genes in predicting infliximab response in Crohn's disease.
  • To conduct a genetic association analysis of polymorphisms within these genes in CD patients.

Main Methods:

  • Genotyping of selected genetic polymorphisms in 350 active CD patients undergoing IFX treatment.
  • Classification of patients into responders and non-responders based on IFX treatment outcomes.
  • Haplotype analysis to identify differences between responder and non-responder groups.

Main Results:

  • Significant differences in haplotypes were observed between IFX responders and non-responders for S100A8-S100A9 (P=0.05), G0S2 (P=0.15), TNFAIP6 (P=0.10), and IL11 (P=0.07).
  • These genetic associations were particularly pronounced in patients with colonic and ileocolonic CD locations.
  • TNFAIP6 showed a significant difference in ileal CD patients.

Conclusions:

  • The findings support the role of the studied gene expression signature in predicting anti-TNF treatment outcomes in CD.
  • The identified genes may play an etiological role in the infliximab response pathway.
  • Genetic association analysis provides insights into the molecular mechanisms underlying IFX response in Crohn's disease.