Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 + 396 G allele (P = 0.02), IL-8 + 396(G/G) and IL-8 + 781(C/T) genotypes (P < 0.001), IL-10 - 1082A allele and IL-10 - 1082(A/A) genotype (P < 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P < 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.

Irritable bowel syndrome: Emerging paradigm in pathophysiology

“…Several studies identified that certain IBS patients may be genetically predisposed to decreased production of IL-10 and subsequent development of low-grade inflammatory manifestations of IBS [99] . In a study done in Mexico, the high IL-10 producer genotype is less prevalent in IBS patients than healthy controls [86] . However, in the abovementioned Netherlands study, IL-10 genotypes were similarly distributed among patients with IBD compared to healthy controls [6] .…”

“…Transient mucosal inflammation is crucial for the manifestation of IBS, despite the original definition of this syndrome that implies the lack of signs of active inflammation [86] . According to the evidence, subsets of IBS patients share genetic susceptibility loci for inflammation.…”

Crosstalk at the mucosal border: importance of the gut microenvironment in IBS

“…197 Also, the genotype combination of high-producer TNF and low-producer IL-10 gene expression has been demonstrated to be more prevalent in patients with IBS than healthy individuals, 198 as well as polymorphisms of the gene encoding the proinflammatory cytokine IL-8. 199 Two independent studies have reported that IBS is associated with genetic polymorphisms of TNFSF15, which encodes the inflammation-related protein TNF ligand superfamily member 15, supporting a role for immune activation in IBS. 200,201 In 2014, it was also demonstrated, using next-generation pair-end sequencing, that patients with IBS-D had decreased mRNA expression of TNFSF15, further confirming the importance of altered expression of this gene in IBS.…”

Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences

“…For example, multiple polymorphisms within the CXCL8 gene are thought to influence susceptibility to the development of irritable bowel syndrome. 99 A collection of research also suggests that polymorphisms at position −251 of the CXCL8 gene enhance susceptibility to a variety of GI disease states. Individuals with adenosine residues at position −251 (−251A) of the CXCL8 gene are thought to be at increased risk of infection from Clostridium difficile, enteroaggregative Esherichia coli, and H. pylori, and following infection, have elevated inflammatory responses and/or more clinically significant disease.…”