An interleukin-4 polymorphism is associated with susceptibility to Clostridium difficile infection in patients with inflammatory bowel disease: results of a retrospective cohort study

Surgery. 2014 Oct;156(4):769-74. doi: 10.1016/j.surg.2014.06.067.

Abstract

Background: Clinical studies have suggested that patients with inflammatory bowel disease (IBD) are at greater risk for developing Clostridium difficile infection (CDI). The purpose of this study was to identify single-nucleotide polymorphisms (SNPs) associated with CDI among IBD patients.

Methods: This retrospective cohort study used our biobank to compare patients with IBD who developed CDI (IBD-CDI) with those who had never contracted CDI (IBD-nCDI). Patients were genotyped for 384 IBD-associated SNPs by microarray. Student t, chi-square, and Fisher exact tests were used. Multivariate logistic regression with Bonferroni correction was used for genotype analysis.

Results: Twenty IBD-CDI (14 with Crohn disease; 6 with ulcerative colitis) and 152 IBD-nCDI (47 CD/105 UC) patients were identified. The interleukin-4-associated SNP rs2243250 was associated with the development of CDI (raw P = .00005/corrected P = .02), with 15 of 20 (75%) CDI-IBD patients harboring the at-risk "A" allele versus 52 of 152 (34%) of IBD-nCDI. When we compared Crohn disease and ulcerative colitis patients separately, rs2243250 initially was associated with CDI in both groups, although clinical relevance was lost after Bonferroni correction.

Conclusion: The interleukin-4 gene-associated SNP rs2243250 was strongly associated with CDI in our IBD population. This SNP may allow for the identification of IBD patients at greater risk for CDI.

MeSH terms

  • Adult
  • Case-Control Studies
  • Clostridioides difficile*
  • Clostridium Infections / etiology
  • Clostridium Infections / genetics*
  • Cohort Studies
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genotyping Techniques
  • Humans
  • Inflammatory Bowel Diseases / complications*
  • Inflammatory Bowel Diseases / genetics
  • Interleukin-4 / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Risk Factors

Substances

  • Genetic Markers
  • Interleukin-4