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

Authors: Jiang, Zhi-Dong1; DuPont, Herbert L.; Garey, Kevin; Price, Margaret2; Graham, Gail2; Okhuysen, Pablo; Dao-Tran, Thanh2; LaRocco, Mark2

Source: The American Journal of Gastroenterology, Volume 101, Number 5, May 2006 , pp. 1112-1116(5)

Publisher: Blackwell Publishing

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Abstract:

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.

(Am J Gastroenterol 2006;101:1112–1116)

Document Type: Research article

DOI: 10.1111/j.1572-0241.2006.00482.x

Affiliations: 1: The University of Texas School of Public Health 2: St. Luke's Episcopal Hospital

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