Association study of forkhead box P3 gene polymorphisms with unexplained recurrent spontaneous abortion

Abstract

Unexplained recurrent spontaneous abortion (URSA) has been suggested to be associated with the failure of fetal–maternal immunological tolerance in which the regulatory T lymphocytes (Tregs) play a crucial role. This study evaluated the association between single-nucleotide polymorphisms (SNPs) in the forkhead/winged helix transcription factor (FOXP3) gene, a key factor for the development and function of Tregs, and URSA, in an Iranian population. In this case–control study, 195 patients with a history of URSA and101 healthy women were included as case and control groups respectively. Four SNPs in the FOXP3 gene, two in the promoter region: −924A/G and −3279C/A, and two intronic, −20G/A and +459T/C, were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The −924A/G (p<0.0001) and −20G/A (p=0.008) polymorphisms were found to be associated with URSA. The respective odds ratios (OR) for bearing −924A/G and −20G/A gene polymorphisms were 4.1 [95% CI 2.3–7.5] and 2.1 [95% CI 1.2–3.6] fold higher in URSA women than those in controls. Thus, there were significant differences in the distribution of A and G alleles of −924A/G and −20G/A between URSA and controls (p=0.001, OR; 3.6 [95% CI 2.1–6.1] and p=0.006, OR; 1.6 [95% CI 1–2.6] respectively). No associations were found for −3279C/A and +459T/C polymorphisms between URSA and controls. These results suggest that polymorphisms of the FOXP3 gene might confer susceptibility to URSA, probably by altering FOXP3 function and/or its expression.