Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 3 2025 09 25 The Effects of two TP53 Polymorphisms on Its Expression and Folding and Association with the Pathogenesis of Polycystic Ovary Syndrome: in-silico analysis 155 161 Mahboobeh Sabeti Akbar-Abad Cellular and Molecular Research Centre, Birjand University of Medical Sciences, Birjand, Iran. Hossein Shahriari Clinical Immunology Research Centre, Zahedan University of Medical Sciences, Zahedan, Iran. Mahdi Majidpour Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran Razieh Akhtar Student Research Committee, Zahedan University of Medical Sciences, Zahedan, Iran. Ramin Saravani Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Mehdi Zandhaghighi Department of Medical Microbiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Ira Khodadad Sheikhzadeh Department of Epidemiology and Biostatistics, Health Promotion Research Centre, Zahedan University of Medical Sciences, Zahedan, Iran. 2025 07 25 2025 09 15 Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy characterized by various reproductive and metabolic abnormalities. The tumor suppressor p53 (TP53) plays a crucial role in cellular stress responses. Alterations in its structure or expression can influence PCOS pathogenesis. This study investigates the association of two genetic variants, rs2287499 and rs1042522, with the expression levels and folding stability of TP53 protein through in-silico analyses. Methods: Utilizing bioinformatics tools, we examined the potential impacts of these single nucleotide polymorphisms (SNPs) on TP53 transcriptional activity, protein structure, and functional integrity. Results: Our findings indicate that the rs2287499 variant significantly influences TP53 expression levels, while rs1042522 is associated with altered protein folding dynamics. These changes may disrupt TP53's normal regulatory functions, contributing to PCOS etiology. Furthermore, our study establishes a framework for integrating genetic variants into the understanding of TP53-mediated mechanisms in PCOS, which could pave the way for developing targeted therapeutic strategies. Conclusion: These results underscore the importance of genetic variants in PCOS hormonal and metabolic dysregulation. https://abi.tums.ac.ir/index.php/abi/article/view/142 https://abi.tums.ac.ir/index.php/abi/article/download/142/113