Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of Membranes

Genes (Basel). 2021 Oct 28;12(11):1725. doi: 10.3390/genes12111725.

Abstract

A prelabor rupture of membranes (PROM) and its subtypes, preterm PROM (pPROM) and term PROM (tPROM), are associated with disturbances in the hemostatic system and angiogenesis. This study was designed to demonstrate the role of single nucleotide polymorphisms (SNPs), localized in CSF2 (rs25881), FLT1 (rs722503), TFPI (C-399T) and TLR9 (rs352140) genes, in PROM. A population of 360 women with singleton pregnancy consisted of 180 PROM cases and 180 healthy controls. A single-SNP analysis showed a similar distribution of genotypes in the studied polymorphisms between the PROM or the pPROM women and the healthy controls. Double-SNP TT variants for CSF2 and FLT1 polymorphisms, CC variants for TLR9 and TFPI SNPs, TTC for CSF2, FLT1 and TLR9 polymorphisms, TTT for FLT1, TLR9 and TFPI SNPs and CCCC and TTTC complex variants for all tested SNPs correlated with an increased risk of PROM after adjusting for APTT, PLT parameters and/or pregnancy disorders. The TCT variants for the CSF2, FLT1 and TLR9 SNPs and the CCTC for the CSF2, FLT1, TLR9 and TFPI polymorphisms correlated with a reduced risk of PROM when corrected by PLT and APTT, respectively. We concluded that the polymorphisms of genes, involved in hemostasis and angiogenesis, contributed to PROM.

Keywords: angiogenesis; genotyping; hemostasis; pPROM; pregnancy; prelabor rupture of membranes (PROM); restriction fragment length polymorphism (RFLP); single nucleotide polymorphism (SNP); tPROM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Fetal Membranes, Premature Rupture / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Humans
  • Lipoproteins / genetics*
  • Maternal Age
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Toll-Like Receptor 9 / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Young Adult

Substances

  • CSF2 protein, human
  • Lipoproteins
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • lipoprotein-associated coagulation inhibitor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1

Supplementary concepts

  • Preterm Premature Rupture of the Membranes