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The role of the IL-12 family cytokines in brain tumourigenesis is an active area of research, but only a few studies have explored the impact of the functional IL12B polymorphisms on brain tumour (BT) risk. The present study aimed to evaluate the possible impact and functional effect of IL12B rs3212227 and rs17860508 on BT susceptibility in adults. We observed a lower frequency of the C-allele variant of the rs3212227 polymorphism among cases with primary BT compared to those with brain metastasis (BrM) and individuals with no benign or malignant tumours under allelic and dominant genetic models. The frequency of the C-allele of rs3212227 was significantly lower in primary BT cases than in controls (16% vs. 26.5% with OR = 0.529, 95%CI: 0.3–0.94, p = .029; ORadjusted=0.442; 95%CI: 0.23–0.87; p = .018). There was no significant association between rs17860508 and BT risk under all analysed genetic models after age and sex adjustment. A significantly higher IL-12p40 serum level in men with primary BT than in women (p = .0007) was found. We observed a sex-specific effect of rs3212227 polymorphism on serum IL-12p40 levels in cases with primary BT in contrast to BrM. The C-allele carriership was associated with higher IL-12p40 in women with primary BT. Serum levels of IL-23 were similar across the patients’ subgroups. The obtained results suggest that the IL12B rs3212227 polymorphism influences the risk for primary BT in contrast to rs17860508 polymorphism and shows a sex-specific functional effect on IL-12p40 levels. Also, the male gender was associated with higher IL-12p40 in cases with primary BT.

Interleukin 12 (IL-12) has a key function in promoting Th1 immune response in the gastrointestinal mucosa. Although cytokine gene polymorphisms are associated with increased risk of gastric cancer (GC), studies on different geographic regions and ethnic groups are not able to draw a consistent result. The current case-control study aims to find out an association between a functional IL-12B rs3212227 polymorphism and the susceptibility and clinical features of the study groups, which are GC, Helicobacter pylori-infected and H. pylori-uninfected intestinal metaplasia (IM). In this study, IL- 12B rs3212227 polymorphism was genotyped in 35 GC cases, 25 H. pylori-infected IM patients, 25 H. pylori-uninfected IM patients, and 25 control subjects. PCR-RFLP analysis was performed to find out and compare the polymorphism profiles of case biopsies. There was statistical significance in genotype distributions and allelic frequencies in GC patients with proximal arrest in stomach (p=0.042). The rs3212227 genotypes and allelic frequencies were not correlated with any of the study groups (p>0.05). Other clinical features examined in the GC patients were also not correlated with the rs3212227 genotypes and allelic frequencies (p>0.05). Current findings suggest that IL-12B rs3212227 polymorphism may play a role in GC development. [ABSTRACT FROM AUTHOR]

Background and Aims Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients. Methods Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG , TNFA , IL10 and IL12B was performed using commercial TaqMan assays. Results We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21–0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (−308G/A), IFNG (+874T/A), IL10 (−1082G/A, −819T/C, −592C/A) were associated with AR or DGF in our patients. Conclusions Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results. [ABSTRACT FROM AUTHOR]

Background: Interleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the impacts of the IL-12 rs3212227 and rs568408 gene polymorphisms on HCC., Methods: We searched PubMed, Embase, Web of Science, and Chinese Knowledge Infrastructure databases for studies on the associations between HCC and IL-12 rs568408 and rs3212227 polymorphisms published prior to 1 May 2020. The effects of the polymorphisms on HCC susceptibility were presented as odds ratios (ORs) and associated 95% confidence intervals., Results: Seven studies were ultimately included, including 2375 cases and 3445 controls. The rs3212227 polymorphism was significantly associated with the risk of HCC in both the dominant model (CC+AC vs. AA, OR=1.22) and the allele model (C vs. A, OR=1.12). Combined analysis of rs568408 yielded a significant relative risk for HCC in the dominant (AA+AG vs. GG, OR=1.13), recessive (AA vs. AG+GG, OR=1.72), allele (A vs. G, OR=1.29), heterozygote (AG vs. GG, OR=1.27), and homozygote models (AA vs. GG, OR 1.17)., Conclusion: The IL-12 rs3212227 and rs568408 gene polymorphisms are associated with an increased risk of HCC.

The aim of this study was to evaluate the possible association of IL12B gene polymorphisms with serum levels of IL-12p40, IL-23 and genetic susceptibility to rheumatoid arthritis (RA) in the Bulgarian population. Genotyping for IL12Bpro (rs17860508) and IL12B A/C - 3' UTR (rs3212227) polymorphisms was performed by polymerase chain reaction (PCR)-based methods in 125 RA patients and 239 healthy controls. The IL-23 and IL-12p40 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). An association was established between the rs17860508 polymorphism and RA susceptibility in Bulgarian population with an increased frequency of rs17860508 minor allele-2 and homozygous genotype-22 in RA patients. The rs17860508 risk RA genotype-22 was also significantly correlated to elevated serum IL-23 in RA patients. Although, there was no association between the rs3212227 and genetic predisposition to RA, significantly increased serum levels of both Il-12p40 and IL-23 were observed in RA patients with the rs3212227 AA genotype. Furthermore, the distribution of haplotypes and genotype combination in our cohort indicated increased RA risk in individuals carrying the rs17860508/rs3212227 2/A haplotype or 2.2/AC+CC combination, while 1/A haplotype or 1.1/AA combination may be protective for RA. In conclusion, our study demonstrates a functional effect of IL12B polymorphisms on IL-12p40 and IL-23 cytokine levels in RA patients and suggests a leading role for IL12B rs17860508 in the genetic predisposition to RA, while IL12B rs3212227 significantly modify the RA risk in Bulgarian population.