Associations of (rs867186), (rs237025), (rs13278372) Polymorphisms and , , Protein Levels with Clinical and Morphological Features of Pituitary Adenomas.

Aim: The aim of this study was to determine associations of (rs867186), (rs237025), (rs13278372) gene polymorphisms and , , protein levels with clinical and morphological features of pituitary adenomas (PAs).

Methods: This case-control study included 459 individuals divided into two groups: a control group ( = 320) and a group of individuals with PAs ( = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for (rs867186), (rs237025), and (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer's recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0".

Results: We found significant differences in (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% ( < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA ( < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold ( < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model ( < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% ( < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% ( < 0.001), and the G allele was less common (13.7% vs. 34.2%, < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold ( = 0.001), and each G allele reduced microadenoma odds by 3.1-fold ( < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model ( < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA ( < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold ( < 0.001), and each G allele reduced odds by 2.2-fold in the additive model ( < 0.001).

Conclusions: The (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors.