Effects of rs929271 SNP in Leukemia Inhibitory Factor Gene on Recurrent Pregnancy Loss, Placental Location and Fetal Gender

Abstract

: Leukemia inhibitory factor (LIF) has an essential role in embryo implantation and placentation. The purpose of this study was to investigate the association of rs929271 SNP on LIF gene with recurrent pregnancy loss (RPL), placental location, and fetal gender in Iranian Azeri women. A total of 300 Azeri women (150 women with at least two recurrent miscarriages and 150 women with at least two healthy deliveries, as the control group) were genotyped for the 3’UTR region T>G SNP on LIF gene (rs929271) by real-time polymerase chain reaction (PCR) method. Placental location and fetal gender were determined by two-dimensional sonography. The analysis showed that female embryos were more likely to abort than males (OR = 1.806, CI = 1.275 to 2.557, P value = 0.00083). The highest odds percentage ratio (OPR) of abortion were in women with fundal (OPR = 1.817) and anterior locations (OPR = 1.483); and the lowest in lower-lying placental locations (OPR = 0.448) (P = 0.0284). In this study, the frequency of T and G alleles were 0.99 and 0.01, respectively, and only two TT and TG genotypes were identified. Women with TG genotype had significantly more recurrent pregnancy loss than TT genotypes (P = 0.0133). The women with TG genotype compared with the TT genotypes were more likely to have low lying (OPR = 2.614) and anterior (OPR = 1.641) placental position. Also, the lowest OPR (0.231) for placental position of TG versus the TT genotype was posterior location (P = 0.0464). The allele G caused more (about 1.9 folds) female embryos than T allele, yet the difference was not significant (P = 0.34). In general, there are indications that the effect of this polymorphism on RPL is repeated due to its effect on the placental location and fetal gender. However, to confirm these results, there is a need to repeat this study in populations with more frequent G allele as well as other polymorphisms on the LIF gene.