The LEPR (853A>G and 511A>G) Transitions may Enhance Idiopathic Recurrent Miscarriage: Evidences Based on Case-control and in silico Studies

Previous studies in human leptin receptor protein (LEPR) signaling are important in the establishment of fetal growth. Idiopathic recurrent miscarriage (IRM) may be the result of abnormal placental and fetal development. Thus single nucleotide polymorphisms (SNPs) of LEPR might be associated with IRM. In our case-control study, which conducted from 2017 to 2018 at the Milad Sari Genetic Detection Center and Razi Hospital (Ghaemshahr, Iran), 140 samples, including 70 cases with history of three or more IRM as before the 22nd week of gestation, and 70 controls with at least two live births and no history of pathologic pregnancies during reproductive period were studied. Polymorphisms of maternal LEPR 853A>G and 511A>G were assessed by PCR-RFLP and SSCP, respectively. Results showed that 853A>G SNP, contained frequent genotype AG (p= 0.002; OR= 0.391; 95% CI= 0.154-0.664) and G allele (p= 0.003; OR= 0.125; 95% CI= 0.032–0.489), revealed a significant protective association with IRM. Primary screening of 511A>G showed that 63 case-samples were AG genotype. PCR directed sequence showed this SNP contained frequent genotype for AG (p= 0.001; OR= 0.57; 95% CI= 0.22-0.147) and G allele (p= 0.006; OR= 0.34; 95% CI= 0.008–0.149), revealed a significant protective association with IRM. Based on our findings, LEPR (853A>G and 511A>G) gene transitions not only might enhance IRM but also could be useful genetic markers in susceptibility and severity of recurrent miscarriage.