CVI Accepts, published online ahead of print on 25 June 2008

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Clin. Vaccine Immunol. doi:10.1128/CVI.00070-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Influence of Host IL-10 Polymorphisms on the Development of Travelers' Diarrhea due to Heat Labile producing Enterotoxigenic Escherichia coli in US Travelers to Mexico

Jose Flores, Herbert L. DuPont, Stephanie A. Lee, Jaime Belkind-Gerson, Mercedes Paredes, Jamal A. Mohamed, Lisa Y. Armitige, Dong-Chuan Guo, and Pablo C. Okhuysen^*

The University of Texas at Houston, Medical School, Texas; St. Luke's Episcopal Hospital, Houston, Texas; The University of Texas at Houston, School of Public Health, Texas; Instituto Nacional de Salud Pública, México; Baylor College of Medicine

^* To whom correspondence should be addressed. Email: Pablo.c.okhuysen{at}uth.tmc.edu.

Background. Up to 60% of US visitors to Mexico develop travelers' diarrhea (TD), mostly due to Escherichia coli that produce heat labile (ETEC-LT) and/or heat stable (ETEC-ST) enterotoxins. Distinct single nucleotide polymorphisms (SNPs) within the IL-10 promoter have been associated with high, intermediate, or low production of IL-10.

Objective. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of travelers' diarrhea in ETEC-LT exposed travelers.

Methods. Sera from US travelers to Mexico collected on arrival and departure was studied for ETEC-LT seroconversion. Pyrosequencing was performed to genotype IL-10 SNPs. Subjects were also studied for other enteropathogens in case of diarrhea.

Results. 121 of 569 (21.3%) travelers seroconverted to ETEC-LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a high IL-10 producing genotype; -1082 GG 83% vs. AA 54% (p 0.02), -819 CC 71% vs. TT 33% (p 0.005), -592 CC 71% vs. AA 38% (p 0.02). Travelers with the haplotype GCC were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% vs. 38%, p 0.002).

Conclusions. Travelers genetically predisposed to produce high IL-10 were more likely to experience symptomatic ETEC TD.

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