Association of rs1570360 and rs2010963 in VEGF and rs2279744 in the MDM2 gene with Recurrent Implantation Failure in Iranian Women

Objective: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. Methods: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. Results: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. Conclusions: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.