Interleukin‐12B‐3′UTR polymorphism in association with IL‐12p40 and IL‐12p70 serum levels and silicosis severity

Abstract

Susceptibility to silicosis and to disease severity is in part genetically determined. In this study, the role of IL-12B-3'UTR polymorphism in susceptibility and severity of silicosis and its influence on IL-12p40 and IL-12p70 serum level were investigated. The quantity of IL-12p40 and IL-12p70 was detected by enzyme-linked immunosorbent assay and the genotype of IL-12B was determined using the polymerase chain reaction-restriction fragment-length polymorphism method. We observed elevated IL-12p40 in contrast to IL-12p70 serum levels in a group of 62 silicosis patients compared with both control groups. In severe silicosis patients, we detected the highest IL-12p40 serum levels (129.1 +/- 67.7 pg mL(-1)); lower in patients with the moderate (94 +/- 41.6 pg mL(-1)), whereas in mild silicosis, the IL-12p40 levels (67 +/- 23.5 pg mL(-1)) was similar to these in healthy donors. According to IL-12B polymorphism, increased serum levels were observed in subjects with AA genotype (103.2 +/- 46.9 pg mL(-1)) compared to silicosis patients with AC genotype (82.7 +/- 38.3 pg mL(-1)). No significant differences of genotype and allele frequencies of the 3'UTR polymorphism were observed between silicosis patients and healthy controls. However, the heterozygous genotype was found approximately five times more frequently in patients with mild and moderate (48% and 52%) silicosis compared to patients with severe silicosis (11%), and that IL-12B polymorphism may contribute to silicosis severity rather than to susceptibility. Our data demonstrated that elevated serum IL-12p40, independently of IL-12p70 levels, is associated with severity of silicosis, and suggested that IL-12p40 profibrotic activity may contribute to silicosis severity.

Correlation between TNF-alpha and IL-12p40-containing cytokines in silicosis

“…The same dependence was observed for IL-12p40 serum levels and this was reported in our previous study (Stanilova et al, 2007). However, serum levels of IL-23 and IL-12p70 were not associated with severity of silicosis.…”

“…Kapachi et al (1995) reported that TGF-b or PDGF also have pro-fibrotic activity and Huaux et al (2002) indicated the profibrotic properties of IL-12p40. Although the impact of IL12p40 and IL-12Bpro genotype on silicosis development and progression was present in our previous studies, here we establish an additive and synergist effect of TNF-a and IL-12p40 in silicosis (Stanilova et al, 2007;Stanilova et al, 2008). Furthermore, we broaden our understanding of silicosis pathogenesis including evaluation of IL-23, which contains the same IL-12/ 23-p40 subunit paired with specific IL-23p19 subunit.…”

Molecular characterization of myostatin (MSTN) gene and association analysis with growth traits in the bighead carp (Aristichthys nobilis)

“…In this study, g.2770C [ A in the 3 0 UTR of AnMSTN has extremely significant associations with TL, BL and BW (P \ 0.01) in hatched population of bighead carp. These results support the previous findings that non-coding regulatory variants are more frequently in complex traits [35][36][37][38][39][40]. Significant association between g.2770C [ A and three growth traits in the present study may be explained by two hypotheses, as suggested by Lynch and Walsh [14].…”

Role of Genetic Factors in Pulmonary Disease Susceptibility

“…The minor allele carriers of the IL-12Bpro promoter polymorphism were associated with a protection against susceptibility to silicosis. This was attributed to the higher production of IL-12p40 in homozygous wild-type patients (Stanilova et al, 2008). As demonstrated for other occupational lung diseases, HLA alleles were also found to be related to silicosis pathogenesis.…”

“…IL-12p40 SNPs were also studied in silicosis for their potential influence on inflammatory response by affecting Th1/Th2 cytokine balance. Stanilova et al found an association between IL-12BA/C 3 0 UTR SNP and silicosis severity in Bulgarian miners (Stanilova et al, 2007). The minor allele carriers of the IL-12Bpro promoter polymorphism were associated with a protection against susceptibility to silicosis.…”