Susceptibility of Estrogen Receptor Alpha Gene Polymorphism Towards Uterine Leiomyoma Development

Author(s): Sonia Narwal, Minakshi Vashist, Rohit Kaushik, Kiran Siwach, Reetu Hooda

Background and Objectives: Solid monoclonal tumors in the uterine myometrium are called uterine leiomyomas. These are the third most frequent benign tumors that negatively impact the endometrium and are a significant cause of morbidity in females. Fibroid tumor development is age-dependent, with 70–80% of women having a tumor by the time they are 50. The present study aimed to investigate the association between SNPs in the ESR1 gene and the development susceptibility of uterine leiomyoma. Methods: The present study assessed the role of the rs2077647 SNP on exon 1 and the rs9322331 SNP on intron 1 of the estrogen receptor alpha gene to uterine leiomyoma development susceptibility (using PCR-RFLP followed by agarose gel electrophoresis and Sanger sequencing). Uterine fibroid tissue from 120 women with leiomyoma (who had either a hysterectomy or a myomectomy done), and 120 adjacent myometrium as control samples, were taken to compare the genotype and allele variation frequencies of ESR1 polymorphism. Using the appropriate statistical methods, the strength of the association of ER-α gene polymorphisms between both groups was determined. To the best of our knowledge, this is the first research study aimed to examine the relationship between the polymorphisms of the ESR1 gene and the risk of developing uterine leiomyoma in North-Indian women. Results: An increased frequency of the C/T genotype for rs2077647 SNP and C/C and C/T genotype for rs9322331 SNP was observed in leiomyoma cases and compared with the control group. An increased frequency of the T allele for rs2077647 SNP and the C allele for rs932233 SNP was observed in leiomyoma cases as compared with the control group. For comparison of different variables chi-square test and Fisher’s exact odd ratio were used and a P-value <0.05 was considered statistically significant. GraphPad Prism 8.0.1 (244) and SPSS software version 29.0 for Windows (SPSS Inc., Chicago, IL, USA) were used for statistical analysis. Interpretation and Conclusions: The study indicates the involvement of ER-α gene polymorphisms as a major genetic regulator in uterine leiomyomas development susceptibility.