Genetic Predictors of Pituitary Adenoma Size: Insights from CXCL13 Genetic Variants

Pituitary adenoma (PA) is one of the most common brain tumors, yet its pathogenesis remains unclear. PA can be categorized by size into microadenomas (<10 mm) and macroadenomas (≥10 mm). While microadenomas usually present with mild or isolated endocrine abnormalities, macroadenomas are more likely to cause visual impairment, headache, hypopituitarism, and local invasiveness due to mass effect on surrounding structures. Molecular biomarkers indicate biological and pathological processes or therapeutic responses, offering valuable insights for diagnosis and prognosis. CXCL13, a homeostatic chemokine, primarily induces B-cell chemotaxis, lymphoid tissue organization, and the recruitment of immune cells. CXCL13 gene variants, particularly those affecting expression or function, may influence PA risk, size, invasiveness, and treatment response. Understanding the genetic role of CXCL13 could support personalized treatments and improve prognostic tools for PA management. A case-control study enrolled 170 PA patients and 230 healthy controls. DNA samples from peripheral blood leukocytes were purified by the DNA salting-out method. Singlenucleotide variants (rs355687, rs1566485) were determined using real-time polymerase chain reaction (RT-PCR). Statistical data analysis was performed using the “IBM SPSS Statistics 30.0” program. We found that CXCL13 rs355687 TT genotype vs. CC+CT was associated with about 2.5-fold decreased odds of PA occurrence under the recessive model (OR = 0.406, 95% CI: 0.169-0.974, p = 0.043) and CXCL13 rs1566485 CA genotype vs. CC+AA was associated with about 1.5-fold increased odd of PA occurrence under the overdominant model (OR = 1.552, 95% CI: 1.041-2.312, p = 0.031). Binary logistic regression analysis revealed that CXCL13 rs1566485 CA genotype vs. CC+AA was associated with about 1.8-fold increased odds of macro PA occurrence under the overdominant model (OR = 1.751, 95% CI: 1.114-2.751, p = 0.015). Conclusions: Our findings show that the CXCL13 rs355687 TT genotype significantly reduces the odds of PA occurrence, suggesting a potential protective effect. In contrast, the rs1566485 CA genotype increases the risk of PA development and demonstrates an even stronger association with macroadenoma formation. These results indicate that CXCL13 genetic variation, particularly rs1566485 CA, may contribute to PA susceptibility and tumor growth dynamics.