Circulating concentration of interleukin-37 in Helicobacter pylori-infected patients with peptic ulcer: Its association with IL-37 related gene polymorphisms and bacterial virulence factor CagA

The immunopathologic responses play a major role in the development of H. pylori (HP)-related gastrointestinal diseases. IL-37 is an anti-inflammatory cytokine with potent suppressive effects on innate and adaptive immune responses. Here, we investigated the IL-37 levels and two single nucleotide polymorphisms (SNPs) including rs3811047 and rs2723176 in IL-37 gene in HP-infected peptic ulcer (PU) patients to identify any relationship. Three groups, including 100 HP-infected PU patients, 100 HP-infected asymptomatic (AS) subjects and 100 non-infected healthy control (NHC) subjects were enrolled to study. Serum IL-37 levels and the genotyping at rs3811047 and rs2723176 were determined using ELISA and SSP-PCR methods, respectively. Significantly higher IL-37 levels were observed in PU patients compared with AS and NHC groups (P < 0.0001). In both PU and AS groups, the CagA+ HP-infected participants displayed higher IL-37 levels compared with those infected with CagA- strains (P < 0.0001). There were significant differences between PU, AS and NHC groups regarding the distribution of genotypes and alleles at rs3811047 and rs2723176 SNPs. The genotype GG and allele G at IL-37 rs3811047 SNP, and the genotype CC and allele C at IL-37 rs2723176 SNP more frequently expressed in PU patients than total healthy subjects (AS + NHC groups) and were associated with an increased risk of PU development (genotype GG: RR = 3.08, P < 0.009; allele G: RR = 2.94, P < 0.01; genotype CC: RR = 5, P < 0.01; and allele C: RR = 5.0, P < 0.02, respectively). The PU patients with allele A at IL-37 rs2723176 SNP expressed higher amounts of IL-37 compared with patients carried allele C at the same position (P < 0.05). In AS carriers and NHC individuals, the IL-37 levels in subjects carried genotype AA or allele A at IL-37 rs2723176 SNP were higher than those carried genotype CC or allele C at the same location (P < 0.01 and P < 0.02 for AS group; P < 0.0001 and P < 0.001 for NHC subjects, respectively). The increased IL-37 levels may be considered as a valuable marker of PU development in HP-infected individuals. The SNPs rs3811047 and rs2723176 were associated with PU development. The CagA status of HP and IL-37 rs2723176 SNP may affect the IL-37 levels.