Association study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 variants in Iranian women with premature ovarian insufficiency: A case-control study

Background: Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease. Objective: This study aims to investigate the polymorphisms of rs243865 in the matrix metallopeptidase 2 (MMP2) gene and rs2234693 and rs9340799 in the estrogen receptor 1 (ESR1) gene with susceptibility to POI in Iranian women under 35 yr. Materials and Methods: This case-control study was performed on 150 women with POI and 150 healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020. The genotyping of ESR1 rs9340799, rs2234693, and MMP2 rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software. Results: Our study revealed the frequency of rs243865 TT, CC genotypes in the MMP2 gene and rs2234693 CC, TT; and rs9340799 GG, AA in the ESR1 gene were more prevalent in the case group compared to the control group. In addition, ESR1 rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the ESR1 gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI. Conclusion: ESR1 rs2234693 and rs9340799 polymorphism were strongly associated with our population’s POI. Key words: Matrix metalloproteinase-2, Estrogen receptor alpha, Primary ovarian insufficiency, Female infertility.