Evaluation of ESR2 rs4986938 (+1730 G/A) Polymorphism As a Potential Genetic Risk Factor for Polycystic Ovary Syndrome

Articles in Press

Document Type : Original Article

Authors
Roghayeh Karimi 1 , 2
Hanieh Shafienia 1 , 3
Seyed Mehdi Hoseini 4
Maryam Behjoo 1
Mahya Rajabi 1
Mohammad Hasan Sheikhha 1
Mahmood Dehghani 2
Fateme Montazeri 1
1 Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Department of Biology, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran
3 Mother and Newborn Health Research Center, Comprehensive Research Institute for Maternal and Child Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4 Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Abstract
Background: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting approximately 18% of reproductive-aged women. Given the crucial role of estrogen in regulating folliculogenesis and ovulation, estrogen receptor (ER) genes, particularly ESR2, are considered primary candidates for investigating the genetic basis of this syndrome. This study was designed to evaluate the frequency distribution of the ESR2 rs4986938 (+1730 G/A) polymorphism in an Iranian population and determine its potential association with PCOS risk and related hormonal/metabolic parameters.
Methods: A case–control genetic association analysis was conducted to compare genotype frequencies of the ESR2 rs4986938 polymorphism between women diagnosed with PCOS and healthy controls. Anthropometric and hormonal variables, including BMI, PRL, LH, and FSH, were assessed across genotypes.
Results: The GA genotype was significantly more prevalent in the PCOS group compared with controls (83% vs. 58%, p < 0.05), indicating a strong association with increased susceptibility. Significant correlations were also observed between the rs4986938 polymorphism and BMI, PRL, LH, and FSH levels.
Conclusion: Our results suggest that the ESR2 rs4986938 polymorphism, and potentially adjacent regulatory regions, may contribute to the etiology of PCOS and its metabolic and reproductive complications. Identification of such genetic variants could support early risk prediction and inform preventive strategies for managing PCOS-related outcomes.
Keywords
Estrogen
ESR2
SNP
Polycystic Ovary Syndrome
Journal of Integrated Maternal and Pediatric Care

Articles in Press, Accepted Manuscript
Available Online from 19 September 2026