IL33 gene polymorphisms and circulating IL-33 levels in pituitary adenoma: a case–control study

Abstract Pituitary adenoma (PA) is common intracranial tumor in which inflammatory mechanisms may contribute to tumor development and progression. Interleukin-33 (IL-33), an immune-related cytokine, has been implicated in tumor-associated inflammation; however, its role in pituitary adenomas remains unclear. This study aimed to investigate the associations between IL33 gene variants (rs11792633, rs1157505, and rs7044343), serum IL-33 levels, and PA occurrence. The study included 195 patients with PA and 235 age- and sex-matched healthy control subjects without a history of PA or other pituitary disorders. Associations between IL33 polymorphisms (rs11792633, rs1157505, and rs7044343), serum IL-33 concentrations, and PA risk were evaluated, as well as relationships with clinical characteristics, including tumour size, hormonal activity, invasiveness, and recurrence. Genomic DNA was extracted from peripheral venous blood samples and genotyped using real-time polymerase chain reaction. Serum IL-33 levels were measured by enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using R software (version 4.1.2). A nominal association was observed for rs11792633; however, it did not remain statistically significant after correction for multiple testing and should be interpreted cautiously because of a marginal deviation from Hardy–Weinberg equilibrium in the control group. No statistically robust associations were identified for the three investigated IL33 variants. Serum IL-33 concentrations were significantly higher in patients with PA than in controls (median (IQR): 7.57 (3.15) vs. 5.81 (3.27) pg/mL; p = 0.00026). No significant associations were observed between serum IL-33 concentrations and the evaluated clinical characteristics. The investigated IL33 variants were not robustly associated with PA susceptibility after correction for multiple testing. Serum IL-33 concentrations were higher in patients with PA than in controls; however, the source, disease specificity, and clinical relevance of this elevation remain uncertain.