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Associations between IGFBP1 gene polymorphisms and the risk of preeclampsia and fetal growth restriction
Xianglan Peng1, Dong He2, Rui Peng1
1Department of Obstetrics and Gynecology, Center for Reproductive Medicine/Department of Fetal Medicine and Prenatal Diagnosis/BioResource Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
Insights
The Insulin-like Growth Factor Binding Protein 1 (IGFBP1) gene single nucleotide polymorphism (SNP) rs1065780A > G is associated with a reduced risk of preeclampsia (PE). The G allele may improve pregnancy outcomes by increasing IGFBP1 protein levels.
Area of Science:
- Genetics
- Obstetrics
- Molecular Biology
Background:
- Preeclampsia (PE) pathogenesis involves Insulin-like Growth Factor Binding Protein 1 (IGFBP1).
- The association between IGFBP1 gene single nucleotide polymorphisms (SNPs) and PE susceptibility remains unclear.
Purpose of the Study:
- To investigate the association between IGFBP1 gene SNPs and preeclampsia susceptibility.
- To explore the relationship between different IGFBP1 genotypes and protein levels in preeclampsia.
Main Methods:
- TaqMan genotyping assay used to analyze 229 women with PE and 361 healthy controls.
- ELISA and Immunohistochemistry (IHC) employed to measure IGFBP1 protein levels across genotypes.
- Statistical analysis to determine genotype-phenotype correlations.
Main Results:
- IGFBP1 SNP rs1065780A > G was linked to a decreased risk of PE, with GG and AG genotypes showing lower risk than AA.
- In the PE group, the G allele correlated with higher fetal birth weight, lower diastolic blood pressure, and reduced ALT/AST levels.
- The G genotype was less frequent in severe PE and associated with lower allele G levels in PE patients with fetal growth restriction (FGR).
- SNP rs1065780A > G increased IGFBP1 protein levels in plasma and decidua of PE patients.
Conclusions:
- The IGFBP1 rs1065780 G allele is associated with a lower risk of developing preeclampsia in Chinese Han women.
- This G allele may confer improved pregnancy outcomes, potentially through elevated IGFBP1 protein levels.
Abstract:
IGFBP1 plays a critical role in the pathogenesis of preeclampsia (PE), but the association between single nucleotide polymorphism (SNP) of IGFBP1 gene and PE susceptibility has not yet been determined. In our study, 229 women with PE and 361 healthy pregnant (non-PE) women were enrolled to investigate its association via TaqMan genotyping assay. In addition, the protein levels of IGFBP1 under different genotypes were explored by ELISA and IHC. We found that IGFBP1 SNP rs1065780A > G was associated with an decreased risk for PE. Women with GG (P = 0.027) or AG (Padj. = 0.023) genotype manifested a significantly lower risk for PE compared to women with AA genotype. In PE group, women carrying G allele exhibited greater fetal birth weight, lower diastolic BP, and lower levels of ALT and AST. The G genotype was found significantly less frequently in the severe preeclampsia (SPE) group than in the non-PE group (GG vs. AA, P = 0.007; G vs. A, P = 0.006). Additionally, women in the PE group who experienced fetal growth restriction (FGR) reflected a lower level of the allele G than did the non-FGR group (P = 0.032); this was not the case for the non-PE group.Rs1065780A>G elevated IGFBP1 protein level in plasma and decidua in PE group. In conclusion Chinese Han women with the SNP IGFBP1 rs1065780 occupied by G exhibited a lower risk of developing PE relative to women with the A genotype and augured for improved pregnancy outcomes through elevation of IGFBP1 protein level.
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