Association of genetic variants in Estrogen receptor (ESR)1 and ESR2 with susceptibility to recurrent pregnancy loss in Tunisian women: A case control study.

Estrogen receptor (ER) signaling is key regulator for maintaining successful pregnancy. Several research suggested that genetic variation in ER genes (ESR)1 and ESR2 is associated with the susceptibility to unexplained recurrent pregnancy loss (RPL), often with inconclusive results. In this study, we investigate the relationship between ESR1 and ESR2 polymorphisms and idiopathic RPL. A total of 444 patients with RPL, defined as three or more consecutive pregnancy losses of unknown etiology, and 446 control women were recruited to the study and their genotypes for ESR1-rs2234693, ESR1-rs3020314, and ESR2-rs928554 variants were determined using allelic exclusion method on real-time polymerase chain reaction. Minor allele frequencies (MAF) of tagging SNPs ESR1 rs2234693 and rs3020314, and ESR2 rs928554 were not significantly different between RPL cases and control women. Considerable higher frequencies of homozygous (2/2) ESR1 rs2234693 genotype carriers were seen between patients vs. control women, which maintained after controlling for age, body mass index (BMI), and menarche. ESR1 haplotype analysis demonstrated two common haplotype (rs2234693-rs3020314) with no linkage disequilibrium between both polymorphisms, and no 2-locus haplotype linked with RPL risk was revealed. The present study confirmed a significant association of specific ESR1 variant (rs2234693) with an increased risk of RPL, further supporting a role for ESR1 as an important candidate locus inducing RPL.