IL-1 Polymorphism and Helicobacter pylori Infection Features: Highlighting VNTR's Potential in Predicting the Susceptibility to Infection-Associated Disease Development.

Genetic polymorphisms at the IL-1 cluster are associated with increased Helicobacter pylori (H. pylori)-associated disease risk in an ethnically dependent manner. Due to the corroborated role of IL-1ß in H. pylori infection progression, our aim is to depict the impact of IL1B rs1143627 and rs16944 as well as the IL1RN variable number of identical tandem repeats (VNTR) on the clinical and biological features of Moroccan H. pylori-infected patients. A total of 58 patients with epigastralgic pain were referred to the gastroenterology department for histopathological and clinical analysis. DNA extraction from antrum and fundus biopsies and PCR-RFLP were performed to detect polymorphisms. As a result, VNTR was significantly associated with IL-1ß antrum levels (p-value = 0.029), where the *1/*4 genotype showed a positive association with upregulated cytokine levels in the antrum and was clustered with H. pylori-infected patients' features and higher levels of IL-1ß in the antrum and fundus. Likewise, *1/*1 genotype carriers clustered with severe gastritis activity and H. pylori density scores along with low levels of IL-1ß in the antrum and fundus, while the *1/*2 genotype was clustered with non-infected-patient features and normal IL-1ß levels. In conclusion, VNTR might be an interesting predictor to identify patients at risk of developing H. pylori-associated pathologies.

Gastric IL-1ß, IL-8, and IL-17A expression in Moroccan patients infected with Helicobacter pylori may be a predictive signature of severe pathological stages.

INTRODUCTION: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, leading to pro-inflammatory cytokines production and immune cells recruitment. Various studies have shown that there are ethnic- and population-related differences in the expression of these cytokines. Although the H. pylori infection is a major public health problem in Morocco, to our knowledge, no study has been carried out in gastric cytokine expression from H. pylori-infected Moroccan patients. Thus we aimed to (i) determine the IL-1ß, IL-8 and IL-17A gene expression in gastric biopsies from Moroccan patients infected with H. pylori, and (ii) to determine the cytokine signature of each pathological stages associated with this infection. MATERIAL AND METHODS: 71 patients with epigastralgic pain were included in this study. The H. pylori detection on gastric biopsies was performed by histopathological and PCR analysis. The IL-1ß, IL-8 and IL-17A mRNA expression in the antrun and fundus biopsies was performed by RT-qPCR. RESULTS: The histopathological and PCR analyses revealed that 87.32% of the patients were infected with H. pylori. IL-1ß mRNA expression was significantly lower in the antral mucosa of H. pylori-infected patients (p = 0.0038) than in the uninfected while there was no significant difference in the expression of IL-8 and IL-17A mRNA. The expression of the three cytokines was higher in the fundic mucosa of H. pylori-infected patients than in the uninfected patients, but only IL-8 and IL-17A expression reached statistical significance (p = 0.042 and p = 0.0179 respectively). Furthermore, the multivariate predictive analysis highlighted a cytokine signature that may predict metaplasia during the infection progression that involves a specific down-regulation of IL17A and an up-regulation of IL1ß in antral and fundic metaplasia respectively.