The Study On PTTG1Polymorphism And Haplotypes With The Susceptibility Of Pituitary Tumor

PTTG1is a member of the pituitary tumor transforming gene family, as a mammalian securin protein, exhibits a cell cycle-dependent expression pattern and is subject to ubiquitin-mediated degradation at the end of metaphase. PTTG1overexpression has been reported in a variety of endocrine-related tumors, especially pituitary, thyroid, breast, ovarian, and uterine tumors, as well as nonendocrine-related cancers involving the central nervous system, pulmonary system, and gastrointestinal system. PTTG1functions in cell replication, DNA damage/repair, organ development, and metabolism. Partially elucidated mechanisms of PTTG1action include protein-protein regulation, transactivation activity, and paracrine/autocrine regulation. The expression of PTTGl was negative in normal pituitary, but increased in most of the pituitary tumors. PTTG1-related growth factor activation is closely related to the development of pituitary tumors. All this shows that PTTG1plays a very important role in the pathogenesis of pituitary tumor.Currently on the PTTG1haplotypes and susceptibility to sporadic pituitary tumors has not been reported correlation. We hypothesized that PTTGl single nucleotide polymorphisms (SNPs) and haplotypes may be associated with the susceptibility of Hunan sporadic pituitary tumors, and studied on this hypothesis. We genotyped five PTTG1haplotype-tagging SNPs (htSNP) by PCR-RFLP assays in a case-control study, which included280Han Chinese patients diagnosed with pituitary adenoma and280age-, gender-and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNPs. No significant differences in allele and genotype frequencies of the htSNPs were observed between pituitary adenoma patients and controls, indicating that none of the individual PTTG1SNPs examined in this study is associated with the risk of pituitary adenoma. In addition, no significant association was detected between the reconstructed PTTG1haplotypes and pituitary adenoma cases or the controls. But after the histological classification, p value was observed close to0.05in the "non-functioning pituitary tumor"(NCA). It suggest if we continue to increase the sample size, it is likely to obtain statistically significant results. This is the first report on the association of PTTG1haplotypes with the risk of pituitary adenoma based on a solid study; it will provide an important reference for future studies on the association between genetic alterations in PTTG1and the risk of pituitary adenoma or other tumors. In addition, this is the first inference on the association of PTTG1haplotypes with the risk of "non-functional pituitary tumor", which the research direction for us to further expand the samples to obtain meaningful results.