A single-nucleotide polymorphism in the gene encoding osteoprotegerin, an anti-inflammatory protein produced in response to infection with diarrheagenic Escherichia coli, is associated with an increased risk of nonsecretory bacterial diarrhea in North American travelers to Mexico

Background. Osteoprotegerin (OPG), an immunoregulatory member of the TNF receptor superfamily, is expressed in inflamed intestinal mucosa. We investigated whether OPG is produced by intestinal epithelial cells and tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the gene encoding...

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Bibliographic Details
Published in:The Journal of infectious diseases 2009-02, Vol.199 (4), p.477-485
Main Authors: Mohammed, Jamal A., DuPont, Herbert L., Jiang, Zhi-Dong, Flores, Jose, Carlin, Lily G., Belkind-Gerson, Jaime, Martinez-Sandoval, Francisco G., Guo, Dongchuan, White, A. Clinton, Okhuysen, Pablo C.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Analysis of Variance
Bacteriology
Biological and medical sciences
Cell Line
Chi-Square Distribution
Diarrhea - epidemiology
Diarrhea - genetics
Diarrhea - immunology
Diarrhea - microbiology
Escherichia coli
Escherichia coli - isolation & purification
Escherichia coli Infections - epidemiology
Escherichia coli Infections - genetics
Escherichia coli Infections - immunology
Escherichia coli Infections - microbiology
Feces - chemistry
Feces - microbiology
Female
Fundamental and applied biological sciences. Psychology
Genetic Predisposition to Disease
Humans
Infectious diseases
Inflammation - microbiology
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Male
Medical sciences
Mexico
Microbiology
Middle Aged
Miscellaneous
Osteoprotegerin - genetics
Osteoprotegerin - metabolism
Polymorphism, Single Nucleotide
Risk Factors
Travel
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Summary:Background. Osteoprotegerin (OPG), an immunoregulatory member of the TNF receptor superfamily, is expressed in inflamed intestinal mucosa. We investigated whether OPG is produced by intestinal epithelial cells and tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the gene encoding OPG (TNFRSF11B) are associated with traveler's diarrhea (TD) among North American travelers to Mexico. Methods. OPG concentration was measured in the supernatants of T84 cells infected with various diarrheagenic Escherichia coli pathotypes. Genotyping was performed for 4 SNPs in the OPG gene for 968 North American travelers with or without TD. Stool samples from travelers with TD were evaluated for the presence of enteric pathogens. Results. T84 cells produced higher OPG levels in response to infection with various diarrheagenic E. coli pathotypes than with E. coli controls (P < .05). A SNP in the exon 1 region of the OPG gene (OPG + 1181G>C) was associated with TD in white travelers who stayed in Mexico for >1 week during the summer (P = .009) and for TD due to nonsecretory pathogens (P = .001). Conclusions. Our study suggests that OPG is secreted by intestinal epithelial cells in response to enteropathogens and that a polymorphism in the OPG gene is associated with an increased susceptibility to TD.
ISSN:0022-1899
1537-6613
DOI:10.1086/596319