Genetic and statistical analysis of ESR1 variants in endometriosis-related infertility: a case–control study from South India

Abstract Background Endometriosis, defined by the abnormal growth of endometrial-like tissue outside the uterus, impacts 6–10% of women of reproductive age and is a significant contributor to infertility. The Estrogen Receptor 1 ( ESR1 ) gene is integral to estrogen-dependent signalling pathways, and variations in this gene have been associated with an increased susceptibility to endometriosis. Methods This study investigated the relationship between two polymorphisms in the ESR1 gene (rs9340799 and rs2234693) and infertility associated with endometriosis in South Indian women. The research involved three groups: infertile women diagnosed with endometriosis, infertile women without the condition, and fertile women serving as controls. Genotyping was performed using PCR, and statistical analyses assessed genotype distributions. Additionally, in silico analyses were conducted using GeneMANIA and STRING to examine ESR1 -related gene–gene and protein–protein interaction networks. Results Among the 163 subjects studied, no significant association was observed between either ESR1 SNP and infertility related to endometriosis across all genetic models. In silico analysis revealed that ESR1 participates in biologically meaningful networks, interacting with multiple genes and proteins involved in hormonal signalling, transcriptional regulation, and reproductive functions, supporting its functional relevance in endometriosis pathways. Conclusion Although ESR1 variants rs9340799 and rs2234693 were not statistically associated with endometriosis-related infertility in this population, bioinformatics analyses underscored ESR1 's role in regulatory networks related to estrogen signalling. These findings warrant further large-scale and functional studies integrating both genetic association and molecular pathway data to better understand ESR1 's contribution to endometriosis.