The Effects of two TP53 Polymorphisms on Its Expression and Folding and Association with the Pathogenesis of Polycystic Ovary Syndrome: in-silico analysis

Mahboobeh Sabeti Akbar-Abad; Hossein  Shahriari; Mahdi  Majidpour; Razieh  Akhtar; Ramin  Saravani; Mehdi  Zandhaghighi; Khodadad  Sheikhzadeh

doi:10.18502/abi.v3i3.20588

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, Iran.
Khodadad Sheikhzadeh Department of Epidemiology and Biostatistics, Health Promotion Research Centre, Zahedan University of Medical Sciences, Zahedan, Iran.

DOI: https://doi.org/10.18502/abi.v3i3.20588

Keywords: TP53, PCOS, Bioinformatics, rs1042522, rs2287499

Abstract

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. We aim to use in-silico analyses to predict the effects of the rs2287499 and rs1042522 genetic variants on the expression and structural stability of the TP53 protein.

Methods: This study investigated the association of two genetic variants, rs2287499 and rs1042522, with the expression levels and folding stability of TP53 protein through in-silico analyses. Utilizing bioinformatics tools (VMD, WebLogo and PROMO), we examined the potential impacts of these variants on TP53 transcriptional activity, protein structure, and functional integrity.

Results: Our findings indicate that the rs2287499 variant significantly influences TP53 expression level, while rs1042522 is associated with altered protein folding dynamics. These changes may disrupt TP53 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