A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection.
BACKGROUND
Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection (CDI). We hypothesized that a common single-nucleotide polymorphism (SNP) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI.


METHODS
This was a prospective cohort study of hospitalized adult patients with CDI who were admitted to a large, university-affiliated medical center from 2007 through 2008. Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI (defined as a return of diarrhea that required treatment after initial symptom resolution). DNA was isolated from blood samples, and genetic sequencing was performed using polymerase chain reaction and pyrosequencing. The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics.


RESULTS
Ninety-six patients with a mean (± standard deviation) age of 61 ± 16 years (54% of whom were female and 63% of whom were white) were identified. The overall incidence of recurrent CDI was 24%. IL-8 allele frequency was similar to previously reported findings (for A/A, 27%; for A/T, 53%; and for T/T, 20%). The incidence of recurrent CDI was 38% in patients with the A/A allele and 19% in all other patients (relative risk, 2.1; 95% confidence interval, 1.04-4.13) (P = .043).


CONCLUSIONS
This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI. Our results could offer risk stratification for patients at high risk for recurrent CDI.
University of Houston College of Pharmacy, Houston, Texas, USA. kgarey@uh.edu
Kevin W
KW
Garey
Zhi-Dong
ZD
Jiang
Shashank
S
Ghantoji
Vincent H
VH
Tam
Vaneet
V
Arora
Herbert L
HL
Dupont
D000368:Aged; D016360:Clostridioides difficile / Q000276:immunology* / Q000472:pathogenicity; D015331:Cohort Studies; D004761:Enterocolitis, Pseudomembranous / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006760:Hospitalization; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D017422:Sequence Analysis, DNA
C508606:CXCL8 protein, human; D016209:Interleukin-8