Genetic Susceptibility to EnteroaggregativeEscherichia coliDiarrhea: Polymorphism in the Interleukin‐8 Promotor Region

Abstract

Enteroaggregative Escherichia coli (EAEC) infection can be identified in 26% of travelers with diarrhea and is associated with fecal interleukin (IL)-8 production. We hypothesized that single-nucleotide polymorphisms (SNPs) in the IL-8 gene are associated with EAEC-related symptoms. Fecal IL-8 production and IL-8 SNPs at 5 loci were identified in 69 US students who remained in Mexico for 5 weeks; 23 subjects had EAEC-associated diarrhea, 7 were asymptomatic EAEC carriers, 22 had nonspecific diarrhea, and 17 were asymptomatic without an enteropathogen. The chances of having EAEC-associated diarrhea were significantly increased among those with the AA genotype at the -251 position (odds ratio [OR], 208.51; 95% confidence interval [CI], 28.5-1525.36) and among those with AT genotype (OR, 14.3; 95% CI, 1.98-105.74), compared with those with the TT genotype at the -251 position. Among subjects with EAEC-associated diarrhea, the AA genotype at the -251 position produced greater concentrations of fecal IL-8 than those with the AT or TT genotype (P=.0053). In the present study, the AA genotype at the -251 position was associated with the occurrence of EAEC-associated diarrhea and increased levels of fecal IL-8.

Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility

“…23 However, the association with haplotype 2 was not reproduced in the context of these other disease states though this may have been due to the smaller sample size used in these studies. 22,23 We reported that association between the IL-8 À251A allele and RSV-induced bronchioilitis was further refined by halpotype analysis which suggested that the functional allele might lie on chromosomes of haplotype 2 and that the À251A may not be the functional SNP.…”

“…23 However, the association with haplotype 2 was not reproduced in the context of these other disease states though this may have been due to the smaller sample size used in these studies. 22,23 We reported that association between the IL-8 À251A allele and RSV-induced bronchioilitis was further refined by halpotype analysis which suggested that the functional allele might lie on chromosomes of haplotype 2 and that the À251A may not be the functional SNP. 9 We have examined the À251 SNP through transient transfection experiments and found higher luciferase expression for the 1409(251T) construct after stimulation with TNF, but no difference between the 1409(251T) and 1409(251A) constructs when the fold changes of stimulated over nonactivated cells were compared.…”

“…Since the publication of the original association studies for the IL-8 À251A allele 8,9 that same allele has been associated with susceptibility to tuberculosis 22 enteroaggregative E. Coli diarrhea, 23 prostate cancer, 24 and greater IL-8 protein production. 23 However, the association with haplotype 2 was not reproduced in the context of these other disease states though this may have been due to the smaller sample size used in these studies.…”

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia

“…It is likely that small changes in the expression or function of these key components can perturb the delicate balance between circulating cytokines and thus, modulate the inflammatory response, which in turn, could impact susceptibility to infectious complications. 12,14,15 Others have reported that common polymorphisms in the genes of the lysosomal enzyme myeloperoxidase (MPO) and the human chitinolytic enzyme chitotriosidase (CHIT) have been associated with bacterial infection in marrow transplantation and in a region endemic for a filarial parasite. 16,17 Similarly, common variants in the low-affinity Fc receptor (FCGR2A), and the toll-like receptors 2 and 4 (TLR2 and TLR4) have been associated with immunological complications as well as bacterial and fungal infections.…”

Distribution of CXCR2 +1208 T/C gene polymorphisms in relation to opportunistic infections among HIV-infected patients in Limpopo Province, South Africa

“…Of the different subclasses of chemokines, the CXC family of chemokines are particularly important in the initiation and amplification of inflammatory diseases (Chapman et al, 2009) such as tuberculosis (TB) (Otsuka et al, 2005), diarrhea (Jiang et al, 2003), chest pain (Stadtmann and Zarbock, 2012), and loss of appetite, which eventually lead to unexplained weight loss. The CXCR2 chemokine receptor is a glycoprotein-coupled receptor found primarily on the surface of leukocytes and binds to interleukin-8 (IL-8) with high affinity.…”