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 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.
Mohamed
Jamal A
JA
Division of Infectious Diseases, The University of Texas Medical School, Center for Infectious Diseases, Baylor College of Medicine, Houston, TX, USA.
DuPont
Herbert L
HL
Jiang
Zhi-Dong
ZD
Flores
Jose
J
Carlin
Lily G
LG
Belkind-Gerson
Jaime
J
Martinez-Sandoval
Francisco G
FG
Guo
Dongchuan
D
White
A Clinton
AC
Okhuysen
Pablo C
PC
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002460:Cell Line; D016009:Chi-Square Distribution; D003967:Diarrhea / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D008800:Mexico; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014195:Travel
D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human