Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of
Wioletta Izabela Wujcicka1, Marian Kacerovsky2,3, Michał Krekora4,5
1Scientific Laboratory of the Center of Medical Laboratory Diagnostics and Screening, Polish Mother's Memorial Hospital-Research Institute, 281/289 Rzgowska St., 93-338 Lodz, Poland.
Insights
Certain gene polymorphisms influence the risk of prelabor rupture of membranes (PROM). Specific combinations of single nucleotide polymorphisms (SNPs) in genes related to hemostasis and angiogenesis can increase or decrease PROM risk.
Area of Science:
- Obstetrics and Gynecology
- Genetics
- Molecular Biology
Background:
- Prelabor rupture of membranes (PROM), including preterm PROM (pPROM) and term PROM (tPROM), is linked to disruptions in hemostasis and angiogenesis.
- Understanding the genetic factors contributing to PROM is crucial for identifying at-risk pregnancies.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in CSF2, FLT1, TFPI, and TLR9 genes and the risk of PROM.
- To determine if specific genotypes or combinations of SNPs in these genes are correlated with PROM development.
Main Methods:
- A case-control study involving 360 women (180 PROM cases, 180 controls) with singleton pregnancies.
- Genotyping of SNPs in CSF2 (rs25881), FLT1 (rs722503), TFPI (C-399T), and TLR9 (rs352140) was performed.
- Statistical analysis was conducted to assess the correlation between genotypes, haplotypes, and PROM risk, adjusting for clinical parameters.
Main Results:
- Single-SNP analysis did not reveal significant differences in genotype distribution between PROM cases and controls.
- Specific combined SNP variants (e.g., TT for CSF2/FLT1, CC for TLR9/TFPI, TTC, TTT, CCCC, TTTC) were associated with an increased risk of PROM.
- Other combined variants (e.g., TCT, CCTC) showed a correlation with a reduced risk of PROM after adjustments.
Conclusions:
- Polymorphisms in genes involved in hemostasis and angiogenesis play a role in the etiology of PROM.
- Combinations of SNPs in CSF2, FLT1, TFPI, and TLR9 may serve as genetic markers for predicting PROM risk.
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.
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