The transcription factor Forkhead Box P3 gene variants affect idiopathic recurrent pregnancy loss

Abstract

Introduction: Forkhead Box P3 (FOXP3) is an essential transcription factor for the induction and development of Tregs. It plays an important role in regulation and suppression of immune responses. We tested whether FOXP3 gene variants are associated with idiopathic recurrent miscarriages (IRM).

Methods: We included 200 women with at least three unexplained spontaneous abortions before twentieth week of gestation and 300 healthy parous women. The detection of genetic variants of rs2232365, and rs5902434 SNPs were carried-out by using polymerase chain reaction (PCR) with sequence-specific primers, while rs3761548 and rs2294021 SNPs were genotyped by PCR followed by RFLP analysis. The logistic odds ratios (ORs) of idiopathic RM risk were estimated with a 95% confidence interval (CI) after maternal age adjustment. Multifactor dimension reduction (MDR) analysis was used to evaluate the potential SNP ∼ SNP interactions.

Results: Single marker analysis revealed an increased risk ranged from almost 3-fold-2-fold for rs2232365, rs3761548, rs5902434 and rs2294021 SNPs in IRM cases. The mutant haplotype carriers of rs2232365, rs3761548, rs5902434 and rs2294021 SNPs showed an increased risk of 2.5-fold for IRM cases. Linkage disequilibrium analysis revealed moderate LD between rs2232365, rs3761548, rs5902434 and rs2294021 SNPs. The MDR analysis revealed 6-fold increased risk for IRM cases in four factor models of rs2232365, rs3761548, rs5902434 and rs2294021 SNPs. The maximum testing accuracy, highest cross validation consistency and greater significance was observed in four SNP model.

Discussion: These results suggest that variants of FOXP3 SNPs namely; rs2232365, rs3761548, rs5902434 and rs2294021 may be associated with idiopathic RM.

Keywords: FOXP3 gene; Pregnancy losses; Recurrent miscarriages; Tag single-nucleotide polymorphism; Variants.