Genetic Factors Influencing Pituitary Adenoma in Females: the Role of IL1R3 rs4624606

Pituitary Adenoma (PA) is a benign tumor arising from the anterior pituitary gland (adenohypophysis). It typically exhibits slow and asymptomatic progression in its early stages. Depending on disease duration and the secretory activity of the adenohypophysis, patients may present with diverse clinical manifestations resulting from hormonal imbalances. The exact etiology and pathogenesis of PA remain unclear. It is believed that multiple factors, including environmental influences, hormonal balance and genetic markers, contribute to the disease development. The disorder is more frequently diagnosed in older individuals. Interestingly, women tend to be diagnosed at a younger age than men, who are typically diagnosed later in life. The IL1R3 gene encodes a coreceptor for IL-1 family cytokines involved in immune response regulation. Overexpression of IL1R3 has been associated with tumor development and poor prognosis. We aimed to investigate the potential role of the rs4624606 polymorphism in the development of PA among women. The study included 269 women, divided into three groups: 55 patients with active PA, 27 with inactive PA and 187 healthy controls. DNA was extracted from peripheral blood leukocytes using the DNA-salting out method. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). Data were analyzed using IBM SPSS Statistics 29.0 software. The results showed that the rs4624606 AG genotype, compared to the GG genotype, decreases the odds of developing active PA by 2.2-fold under the codominant genetic model (p = 0.025). The combined AG+AA genotypes, compared to GG, reduce the odds of active PA by 2.2-fold under the dominant model (p = 0.014). When comparing the AG genotype with the combined GG+AA genotypes, the odds of active PA in women decreased 2 times under the overdominant model (p = 0.045). Moreover, the A allele decreased the odds of active PA in women by 1.8-fold under the additive model (p = 0.022). The rs4624606 polymorphism in women is associated with a reduced odds of active PA occurrence, suggesting a potential protective effect of this genetic variant.