| Background:Preeclampsia(PE)is one of the pregnancy-specific diseases that might lead to substantial maternal and fetal morbidity and mortality.The pathogenesis has not been fully elucidated,and genetic factors are one of the key points.IGFBP1 plays a critical role in the pathogenesis of preeclampsia,and the relationship between its nucleotide polymorphisms and the susceptibility to preeclampsia has not been studied so far.Objective:This study aimed to investigate the association of IGFBP1 gene polymorphisms and preeclampsia susceptibility in Chinese Han women and the association of SNPs with pregnancy outcomes exhibited by clinical characteristics and biochemical markers.Methods:1 A total of 229 women with PE and 361 healthy pregnant(CTRL)women of Chinese Han were enrolled from The Third Affiliated Hospital of Guangzhou Medical University from January 2016 to June 2022.The clinical manifestations and related medical history of the subjects were collected,the clinical biochemical tests were collected,and the genomic DNA of peripheral venous blood was extracted.Three SNP locus on IGFBP1 gene were examined via the TaqMan genotyping assay.Statistical analysis was performed using SPSS25.0,and binary logistics regression was applied to analyze the relationship between genotype and susceptibility to preeclampsia.2 Verify the association of IGFBP1 gene polymorphisms with susceptibility to preeclampsia.The protein level of IGFBP1 in peripheral blood plasma was measured by ELISA to analyze the association with gene polymorphisms;placental IGFBP1 protein was detected by immunohistochemistry to analyze the distribution of placental decidual trophoblast cells under different genotypes.Results:1 The observed genotypic distributions were in agreement with the HWE principle in the CTRL group(P>0.05).rs9658194 C>A and rs4619 G>A showed no significant association with susceptibility to preeclampsia.rs1065780A>G was associated with an decreased risk for PE.Women with GG(OR=0.565,P=0.027)or AG(OR=0.615,adj.P=0.023,adjusted by age and BMI)genotype manifested a significantly lower risk for PE compared to women with AA genotype;and the G allele achieved a significantly lower ratio in women with PE(P= 0.026)in the allelic model.2 In the PE group,women carrying the G allele exhibited greater fetal birth weight,lower diastolic BP,and lower levels of ALT and AST.Additionally,fetuses in 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.3 For all the subjects,the peripheral circulating IGFBP1 protein level carrying genotype AG was significantly higher compared to AA,305.096(260.505-328.498)vs.251.755(220.805-291.046),P=0.035,and this difference remained in the preeclamptic group[316.683(289.279-348.510)vs.251.755(224.195-291.046),P=0.014].This differential presentation was absent in the non-gestational group.In placenta,there was no significant difference in decidual IGFBP1 levels between CTRL and preeclamptic groups,P=0.280.For preeclamptic group,significantly high levels of decidual IGFBP1 carrying the AG or GG genotype compared to AA[AG vs.AA:0.072±0.015 vs.0.021± 0.004,P=0.032;GG vs.AA:0.105± 0.021 vs.0.021 ±0.004,P=0.001].In placental trophoblasts,there was no significant difference in either the comparison of CTRL and preeclamptic groups or in the distribution of different genotypes.Conclusion:Our data suggested that 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.This protective effect might act through upregulation of IGFBP1 protein levels in the peripheral circulation and placental decidual tissues. |
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