Foxp3 (−/ATT) Polymorphism Contributes to the Susceptibility of Preeclampsia

Ximing Chen,Ting Gan,Shengqiang Chen,Jianhua Xiao,Zhiqiong Liao,Hongmei Wang

doi:10.1371/journal.pone.0059696

Abstract

ObjectiveTo evaluate the potential influence of Foxp3 polymorphism on preeclampsia (PE) susceptibility, we conducted a case-control study in Han Chinese women.Methods Foxp3 genotyping was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 156 PE patients and 252 age-frequency matched controls. Immunohistochemical staining was used to detect the expression of Foxp3 specific transcription factor in 30 PE and 30 normal pregnant women.ResultsThe positive rate of Foxp3 expression in PE (26.67%) was significant difference from that in normal control (63.33%, P<0.05). The frequency of Foxp3-6054 TT genotype was significantly lower in PE patient than that in control. No significant difference was found in Foxp3-3279 genotypes between PE and control, as well as for the variant allele. The frequency of Foxp3-6054A/−3279C haplotype in PE was significantly higher than that in control (P<0.01), while the frequency of Foxp3 6054T/−3279C haplotype was significantly lower in PE patient than that in control (P<0.01).ConclusionOur findings suggest that the immune suppression function in PE patients is weakened, which may result in the occurrence of PE. Foxp3 polymorphism (rs5902434) may be a potential contributor for the development of PE in Han Chinese women.

Highlights

Preeclampsia (PE) is a severe complication of pregnancy with a worldwide incidence of 2-10%
It has been demonstrated in mouse models that inactivation of forkhead box p3 (Foxp3) results in a deficiency of Treg cells (Tregs), and notable organ specific Foxp3 is a major regulator for the development and function of Tregs [11]
Several previous studies have found an association between Foxp3 gene polymorphisms and autoimmune diseases, such as systemic lupus erythematosus (SLE) [13], autoimmune thyroid diseases (AITDs) [14], type I diabetes (TID) [15], and allergic rhinitis [16]

Summary

Introduction

Preeclampsia (PE) is a severe complication of pregnancy with a worldwide incidence of 2-10% It is one of the leading causes of maternal and perinatal morbidity and mortality. Decreased exposure to semen from the father of the child and preconception increased risk of PE Taken together, these observations indicated that PE may partially mediate by immune system. Less is known about the function of Foxp gene in humans [10] It has been demonstrated in mouse models that inactivation of Foxp results in a deficiency of Tregs, and notable organ specific Foxp is a major regulator for the development and function of Tregs [11]. The decreasd expression of Foxp in preeclampsia demonstrates that the reduction of Tregs numbers may result in the imbanance of immunologic tolerance between the mother and fetus,thereby participating in the pathogenesis of preeclampsia. We undertook a case-control study to determine whether two genetic polymorphisms (rs5902434 del/ ATT and rs3761548 A/C) in Foxp gene are associated with PE risk

Methods

Results

Conclusion