| Summary: | In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the <i>TERF1</i> rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the <i>TNKS2</i> rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the <i>TERF1</i> rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the <i>TNKS2</i> rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the <i>TERF1</i> rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the <i>TNKS2</i> rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the <i>TNKS2</i> rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the <i>TERF1</i> rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the <i>TNKS2</i> rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the <i>TERF1</i> rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the <i>CTC1</i> rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in <i>TERF1</i> and <i>TNKS2</i> genes may play crucial roles in telomere length regulation and disease susceptibility.
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