Association Study of ESR۱ rs۹۳۴۰۷۹۹, rs۲۲۳۴۶۹۳, and MMP۲ rs۲۴۳۸۶۵ 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 ۴۰ 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 rs۲۴۳۸۶۵ in the matrix metallopeptidase ۲ (MMP۲) gene and rs۲۲۳۴۶۹۳ and rs۹۳۴۰۷۹۹ in the estrogen receptor ۱ (ESR۱) gene with susceptibility to POI in Iranian women under ۳۵ yr. Materials and Methods: This case-control study was performed on ۱۵۰ women with POI and ۱۵۰ healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October ۲۰۲۰. The genotyping of ESR۱ rs۹۳۴۰۷۹۹, rs۲۲۳۴۶۹۳, and MMP۲ rs۲۴۳۸۶۵ 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 rs۲۴۳۸۶۵ TT, CC genotypes in the MMP۲ gene and rs۲۲۳۴۶۹۳ CC, TT; and rs۹۳۴۰۷۹۹ GG, AA in the ESR۱ gene were more prevalent in the case group compared to the control group. In addition, ESR۱ rs۲۲۳۴۶۹۳ and rs۹۳۴۰۷۹۹ genotypes showed significant association with the development of the disease in our population. Among ۴ haplotypes for ۲ polymorphisms in the ESR۱ gene, rs۲۲۳۴۶۹۳T/rs۹۳۴۰۷۹۹A haplotype was associated with conferring risk to POI. Conclusion: ESR۱ rs۲۲۳۴۶۹۳ and rs۹۳۴۰۷۹۹ polymorphism were strongly associated with our population’s POI.

Keywords:

Matrix metalloproteinase-۲ , Estrogen receptor alpha , Primary ovarian insufficiency , Female infertility. , ماتریکس متالوپروتئیناز-۲ , گیرنده استروژن-۱ , کاهش زودرس ذخیره­ی تخمدان , ناباروری زنان.