Interferon-gamma (IFN-g) is a pro-inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN-g in (þ874 A/T in intron 1) TT and þ5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-g variants by an allele-specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the þ874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR ¼ 2.588; 95% CI, 1.313-5.104; P ¼ 0.006 for the AA genotype; OR ¼ 1.575; 95% CI, 1.124-2.216; P ¼ 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN-g polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (þ874/ UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN-g þ874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.
Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T-helper 1 (Th1) cytokines such as interleukin-12 (IL-12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL-12p40 cytokine (IL-12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL-12p40. We genotyped IL-12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case-control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL-12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429-0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218-0.900 for the CC genotype). Comparison of IL-12B genotypes and serum levels of the IL-12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL-12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL-12p40 and could possibly contribute to an inherited predisposition to brucellosis.
Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches.
The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.