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

• 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
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/596319

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.