A Common Polymorphism in the Interleukin 8 Gene Promoter Is Associated with Clostridium difficile Diarrhea

OBJECTIVE: Mucosal interleukin 8 (IL-8) and neutrophil recruitment are central to the pathogenesis of Clostridium difficile (CD) toxin-induced diarrhea (CDD). We hypothesized that like other inflammatory mucosal infections, susceptibility to CDD would relate to genetically determined variations in the production of IL-8. METHODS: Fecal IL-8 production and single nucleotide polymorphism (SNP) frequency in the -251 region of the IL-8 gene were determined in hospitalized patients: 42 with CDD, 42 with CD-negative diarrhea, and 41 without diarrhea. Cases and controls were matched by age, length of hospital stay, comorbidity, and receipt of antibiotics. RESULTS: An association was found between the IL-8 -251 A/A allele and occurrence of CDD, 39%versus 16% (OR = 3.26, 95% CI 1.09-9.17) and 17% (OR = 5.50, 95% CI 1.22-24.8) for the two control groups. Comparing results by IL-8 genotype for the CDD cases, median and mean fecal IL-8 levels were significantly higher for the -251 A/A genotype (p = 0.03 for median and 0.001 for mean). CONCLUSIONS: These studies indicate a common SNP in the IL-8 gene is associated with increased susceptibility to CDD and with increased fecal IL-8 in diarrheal stools.