title: An interleukin-4 polymorphism is associated with susceptibility to Clostridium difficile infection in patients with inflammatory bowel disease: results of a retrospective cohort study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Connelly
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: William
authors.initials: W
authors.lastname: Sangster
authors.affiliation: Department of Public Health Sciences, The Pennsylvania State University, Hershey, PA.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Berg
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Harris
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA.
authors.forename: Susan
authors.initials: S
authors.lastname: Deiling
authors.affiliation: Department of Surgery, Division of Colon & Rectal Surgery, The Pennsylvania State University, Hershey, PA. Electronic address: dstewart@hmc.psu.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Stewart
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D015847:Interleukin-4