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.

Association of a single nucleotide polymorphism in the TLR2 gene (rs3804099), but not in the TLR4 gene (rs4986790), with Helicobacter pylori infection and peptic ulcer.

BACKGROUND/AIMS: Toll-like receptors (TLRs), particularly TLR2 and TLR4, take part in elicitation of immune responses against Helicobacter pylori (H. pylori). This study aimed to investigate the relationship between single nucleotide polymorphisms (SNP) rs3804099 in the TLR2 gene and rs4986790 in the TLR4 gene with H. pylori infection and peptic ulcer (PU). MATERIALS AND METHODS: Blood specimens were obtained from 350 individuals, including 100 H. pylori-infected patients with PU, 125 H. pylori-infected asymptomatic subjects (AS), and 125 non-infected healthy subjects (NHS). The DNA was extracted, and the SNPs were determined using ARMS-PCR method. RESULTS: The frequency of CT genotype at TLR2 SNP rs3804099 in both the PU and AS groups was significantly higher than in the NHS group (p<0.05). In total H. pylori-infected individuals (PU+AS), the frequency of the CT genotype at rs3804099 was also significantly higher than in the NHS group (p<0.005). The frequency of the CC genotype at rs3804099 in PU+AS was markedly lower than in the NHS group (p=0.066). PU patients carried CT genotype more frequently than total healthy individuals (AS+NHS) (p<0.03). The distribution of the TT genotype was lower, whereas the frequency of the CT genotype was higher in AS individuals infected with CagA+ strains than those infected with CagA- strains (p<0.03). No significant differences were found among the PU, AS, and NHS groups regarding the genetic differences at rs4986790 in the TLR4 gene. CONCLUSION: These results provide evidence regarding the association of the rs3804099 in the TLR2 gene with H. pylori infection and PU. The rs3804099 may affect vulnerability to H. pylori infection, particularly to CagA+ strains of bacteria.

Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms.

OBJECTIVES: IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. MATERIALS AND METHODS: Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP. RESULTS: The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL-33/IL-12 ratio were significantly higher in patients than the control group (P<0.001). The IL-33 levels and IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and rs1929992 between patients and the control group. No significant differences were observed between subjects with various genotypes at rs3212227 and rs1929992 with respect to related cytokine levels. CONCLUSION: These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy.