Associations between IGFBP1 gene polymorphisms and the risk of preeclampsia and fetal growth restriction

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.

Automated summary

IGFBP1 gene single nucleotide polymorphism is associated with preeclampsia susceptibility. The GG or AG genotypes are associated with a decreased risk of preeclampsia. Women in the preeclampsia group with the G allele have higher fetal birth weight, lower diastolic blood pressure, and lower levels of ALT and AST. Rs1065780A>G raises the level of IGFBP1 protein in plasma and decidua in the preeclampsia group.