Diminished circulating concentration of interleukin-35 in Helicobacter pylori-infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

Background: IL-35 modulates immune and inflammatory responses during infections. Here, we investigated IL-35 levels and a single nucleotide polymorphism, rs3761548, in FOXP3 gene in Helicobacter pylori-infected patients with peptic ulcer (PU), to clarify possible associations. Materials and Methods: This study includes 100 H. pylori-infected PU patients, 100 H. pylori-infected asymptomatic subjects (AS), and 100 noninfected healthy subjects (NHSs). Serum IL-35 levels and the genotyping were determined using ELISA and RFLP-PCR methods, respectively. Results: In PU patients, the IL-35 levels were lower than AS and NHS groups (P <.001). The IL-35 levels in CagA+ H. pylori-infected participants from PU and AS groups were lower than individuals infected with CagA- strains (P <.02 and P <.04, respectively). Women had higher IL-35 levels than men among PU, AS, and NHS groups (P <.0001). In PU patients, AA genotype and A allele at rs3761548 were more frequent than total healthy subjects (AS + NHS groups) and associated with an increased PU risk (AA genotype: OR = 5.51, P <.0001; A allele: OR = 3.857, P <.002). In PU and AS groups, IL-35 levels were lower in subjects displaying AA genotype or A allele than subjects displaying CC genotype or C allele, respectively (P <.0001 and P <.03 for PU patients; P <.001 and P <.02 for AS group, respectively). Conclusions: Decreased IL-35 levels could be involved in PU development in H. pylori-infected individuals. IL-35 levels are affected by CagA status of H. pylori, participants gender, and genetic variations at rs3761548. The AA genotype and A allele at rs3761548 could represent a risk factor for PU development.