Sex-specific functional effect of IL-12 gene polymorphisms in brain tumours

Abstract

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; OR_adjusted=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.

Keywords:

• IL-12p40
• IL-23
• primary brain tumours
• metastatic brain tumours
• rs3212227
• rs17860508

Author contributions

SV, BG and LM were involved in the conception and design; SV, BG, AG, BP, RY and LM planned the experiments; SV, AG, BP, RY and LM performed the analysis; SV, BG, AG, BP, RY and LM were involved in interpretation of the data; BG, AG, BP, and RY were involved in drafting of the paper; SV, and LM revised the manuscript; all authors approved the final version of the paper to be published and are agree to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available upon reasonable request from the corresponding author, LM. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

This work was supported by the Medical Faculty, Trakia University under Grant no. NIP9/2021 and by the Bulgarian Ministry of Education and Science (MES) in the frames of Bulgarian National Recovery and Resilience Plan, Component ‘Innovative Bulgaria’, the Project No.BG-RRP-2.004-0006-C02 ‘Development of research and innovation at Trakia University in service of health and sustainable well-being’.