Polymorphism in Regulatory T-cell (Treg)-Related Genes Is Associated with Unexplained Recurrent Pregnancy Loss

Fadel A Sharif

doi:10.11648/j.ajcem.20160403.15

Abstract

In the absence of confirmed causes for around 50% of recurrent pregnancy loss (RPL) cases this study was conducted in order to investigate the association between single nucleotide polymorphism (SNP) in regulatory T-cell related STAT3 (rs4796793 C/G), FOXP3 (rs3761548 A/C), LIF (rs3753082 T/C), NKG7 (rs71358833 A/G) and CCR5 (rs34418657 G/T) genes and unexplained RPL in a group of Palestinian women residing in Gaza strip. A retrospective case-control study was carried out during the period (August 2015 to March 2016). A total of 200 females, 100 RPL patients and 100 control women without previous history of RPL, aged 20–35 years were included in the study. STAT3 (rs4796793 C/G), FOXP3 (rs3761548 A/C), LIF (rs375082 T/C), NKG7 (rs71358833 A/G) and CCR5 (rs34418657 G/T) polymorphisms were tested by PCR-RFLP. Statistically significant difference existed between RPL cases and controls in terms of the genotypic distribution of the tested polymorphisms. STAT3 CC, FOXP3 AA, LIF CC, NKG7 AA and CCR5 GG genotypes were significantly higher in the RPL group. The tested polymorphisms shape the first elements of immune tolerance-related risk SNPs panel for RPL in the investigated population and may lead to improved therapeutic approaches.

Highlights

Recurrent pregnancy loss (RPL) is currently defined as two or more consecutive pregnancy losses before the 20th week of gestation
LIF (Leukemia inhibitory factor) whose gene is on chromosome 22 (22q12.2) is a cytokine produced by maternal T-cells and has a direct role in the specific regulation of adaptive immune tolerance
This study was designed in order to test whether STAT3, FOXP3, LIF, NKG7 and CCR5 polymorphisms are associated with RPL in Palestinian women

Summary

Introduction

Recurrent pregnancy loss (RPL) is currently defined as two or more consecutive pregnancy losses before the 20th week of gestation. In the face of unknown etiological factor(s), breached immune tolerance is proposed as a potential mechanism underlying unexplained RPL [3] This reportedly includes autoimmune abnormalities (e.g., positive anti-phospholipid, anti-nuclear and anti-microsomal antibodies), increased cellmediated immunity and altered regulatory T-cell level and/or suppressive capacity [4,5]. LIF (Leukemia inhibitory factor) whose gene is on chromosome 22 (22q12.2) is a cytokine produced by maternal T-cells (including Tregs) and has a direct role in the specific regulation of adaptive immune tolerance. NKG7 (Natural killer cell granule protein 7), on chromosome 19q13.41, codes for a cell-surface protein and is predominantly transcribed, under the control of Foxp, in activated Tregs [16] This protein is deemed important for the establishment of immune tolerance [17]. This study was designed in order to test whether STAT3 (rs4796793 C/G), FOXP3 (rs3761548 A/C), LIF (rs3753082 T/C), NKG7 (rs71358833 A/G) and CCR5 (rs34418657 G/T) polymorphisms are associated with RPL in Palestinian women

SNP Genotyping

Results

Discussion