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.
Jiang
Zhi-Dong
ZD
The University of Texas School of Public Health, USA.
DuPont
Herbert L
HL
Garey
Kevin
K
Price
Margaret
M
Graham
Gail
G
Okhuysen
Pablo
P
Dao-Tran
Thanh
T
LaRocco
Mark
M
D016360:Clostridioides difficile; D003967:Diarrhea / Q000235:genetics* / Q000382:microbiology; D004761:Enterocolitis, Pseudomembranous / Q000235:genetics; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
D016209:Interleukin-8