The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.

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Colorectal cancer (CRC) development is strongly associated with innate immune mechanisms and intestinal inflammation. The aim of the study was to investigate the pre-operative serum levels of TNF-α and its correlation with cancer progression and survival in CRC patients taking into account the genotype of –308G/A promoter polymorphism in TNF-α gene (rs1800629). TNF-α –308G/A genotypes of 119 CRC cases and 177 no CRC controls were determined by restriction fragment length polymorphism assay (RFLP-PCR). TNF-α serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Although no significant differences in allele and genotype frequencies between CRC and controls were observed, it should be noted that the minor allele-A and its homozygous genotype were overrepresented among CRC. In addition, allele-A was more frequent in early CRC patients compared to advanced cases. TNF-α serum level was significantly higher in CRC patients than in controls (36.1 ± 8.4 pg/mL vs. 18.66 ± 11 pg/mL; p = 0.0000001). In the subgroup analysis by tumour–node–metastasis stages, the highest TNF-α level was found in stage IV (42.7 ± 12.5 pg/mL) and was significantly elevated compared to earlier stages of CRC and controls. The survival rate of CRC patients with low TNF-α serum level, estimated as median survival, was significantly higher than that of patients with high levels of TNF-α (38.4 vs. 7.761 months; log rank test p = 0.00015) In conclusion, we can affirm that TNF-α affects tumour development along with disease progression which has an impact on the survival of CRC.

A wide array of studies has demonstrated differences in genotype and allele frequencies of cytokine gene polymorphisms depending on ethnicity and race. In this study, the frequency of Taq-I polymorphism in 3 0 untranslated region of IL-12B was investigated in two Bulgarian ethnic groups-Bulgarians and Turkish minority. No significant differences of genotype and allele frequencies were observed between these groups. Genotype distribution in the total group of Bulgarian citizens was: AA (61%), CA (32%) and CC (7%), and the allele frequency of 16974 A allele was 0.77. We also evaluated whether this polymorphism affects IL-12p40 production from human PBMC after stimulation. We demonstrated that association between genotype and IL12p40 production by stimulated PBMC depends on the stimuli used. Our results indicated a significantly decreased IL-12 p40 secretion for the following order of genotypes: AA4CA4CC, after stimulation of PBMC with C3-binding glycoprotein (C3bgp) in contrast to lipopolysaccharide, phytohaemagglutinin and pokeweed mitogen.