Association Of Polymorphisms In The Estrogen Receptors (ESR) With Unexplained Recurrent Spontaneous Abortion (URSA)

Background: Recurrent spontaneous abortion (RSA) is classically defined as two ormore clinical consecutive pregnancy losses before the20th week during the firsttrimester and affects approximately3%of couples trying to conceive. Until now, anumber of risk factors have been associated with RSA, including uterineabnormalities, autoimmune diseases, genetic anomalies, endocrinological abnormalitiesand thrombophilia, but approximately50%of RAS patients are classified as idiopathicunexplained recurrent spontaneous abortion (URSA). Lots of research approaches basedon candidate gene, an increasing number of autosomal candidate genes involved in RSAhave being reported. As the development of molecular biology research, a lot ofresearch shows abortion may related with the abnormal genes, such as endocrinehormone related gene polymorphism, immune system related gene polymorphism,inherited thrombus disease related gene polymorphism, etc.Estrogen, the main female sex hormones, plays a critically physiologic role in themaintenance of primate pregnancy. The effects of estrogen are mediated via two nuclearreceptors estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2). Theestrogen receptors (ER) are the products of separate genes present on distinctchromosomes and display distinct expression patterns. The abnormal genes may lead toall kinds of physiological and pathological abnormalities, including infertility, abortion,tumor (uterus, ovarian, breast, and prostate endometrium), osteoporosis,neurodegenerative disease, cardiovascular disease, insulin resistance, lupuserythematosus, endometriosis and obesity. Since Lehrer shows that eceptor gene polymorphism may relate with recurrent miscarriage, a large number of domestic andforeign research focuses on the estrogen receptor gene and recurrent miscarriage.Objectives: To investigate the association of single nucleotide polymorphisms(SNPs),respectively-located on estrogen receptor (ESR) gene with recurrent spontaneousabortion in chinese population.Methods: The study group consisted of196patients with recurrent spontaneousabortion and182fertile women as control. Anticoagulated venous blood was collectedin EDTA-coated tubes, and DNA extracted using the QIAamp genomic DNA kits. Therelation between four functional polymorphisms PvuII(rs2234693) and XbaI(rs9340799)of ESR1, RsaI(rs1256049) and AluI(rs4986938) of ESR2with RAS were studied byPCR-RFLP and association analysis.Results: The genotype distribution of PvuII, XbaI, RsaI and AluI in the two groupswere analyzed by chi-square analysis through SPSS software. There were nosignificant differences between ESR1, ESR2gene polymorphisms with recurrentspontaneous abortion (χ~2=0.879, P=0.644; χ~2=1.622, P=0.445; χ~2=1.793, P=0.408; χ~2=1.432, P=0.489).Conclusion: The present data indicate that the studied SNPs on ESR1and ESR2genemay not be associated with recurrent spontaneous abortion in chinese population.