Relationship Between Rs3758539 Of Retinol Binding Protein 4 Gene And Genetic Susceptibility To Preeclampsia And Study On The Level Of Serum And The Expression Of RBP4 In Placenta Of Patients

Objective:To study the association between rs3758539 locus of retinol-binding protein 4(RBP4)gene and genetic susceptibility to preeclampsia.To confirm whether rs3758539 locus of retinol-binding protein 4(RBP4)gene is sensitive gene of preeclampsia or not.To provide theoretical evidence for clinical prevention and treatment of preeclampsia.To study the serum level of retinol binding protein 4 and the expression of RBP4 m RNA and protein in placenta.Methods:1.We select 1176 pregnant women with preeclampsia which were classified to case group and 1441 healthy normal delivery women which were classified to control group among several cities and hospitals in Shandong province during the time from January 2015 to December 2019.Draw 3-5ml peripheral venous blood(EDTA)?separate part of peripheral blood and extract DNA.Using Taqman probe real-time PCR to detect the polymorphism of rs3758539 locus polymorphism of RBP4 gene.Using Sanger sequencing method to examine the accuracy of Taqman probe real-time PCR.Using Hardy-Weinberg equilibrium Law to detect population genetic representativeness.The general clinical differences between the two groups were compared by independence t-test.The general clinical differences between the multigroups were compared by one-way analysis of variance.Pearson-?~2-test was used to compare the distribution of genotypes and alleles between the two groups.The relative risk was expressed by OR value and 95% confidence interval,which was statistically significant when bilateral P < 0.05.2.Randomly selected 39 healthy normal delivery women and 32 pregnant women with preeclampsia which were admitted in hospital during the time from September 2018 to December 2019,draw peripheral venous blood and separate serum.Using Enzyme linked immunosorbent assay to detect the serum level of retinol binding protein 4 in women with preeclampsia and healthy normal delivery women;After delivery,collecting the placenta tissue and extracting RNA.To quantitatively analyze the expression of RBP4 m RNA in placenta of pregnant women by Real-Time PCR.Results:1.Sanger sequencing method proved that Taqman probe real-time PCR detect the result of single nucleotide polymorphism was right.The results of Hardy-Weinberg genetic balance test showed that the subjects in this study could represent well population.Compared with the control group,there was no significant difference in age,pregnancy and abortion times between the PE group and the control group,but the gestational week of delivery was significantly earlier,the fetal birth weight was significantly lower,and the systolic blood pressure and diastolic blood pressure were significantly higher in the PE group.There is a significant difference in genotype distribution of RBP4 gene rs3758539 locus between the case group and the control group(P<0.05),the difference in gene frequency between the case group and the control group is not significant.There is no significant difference in dominant subgroup(P<0.05)between two groups;the difference in recessive subgroup is not significant.There is a significant difference in genotype distribution of RBP4 gene rs3758539 locus between the early-onset PE groups and the control group(P<0.05),the gene frequency of that is not significant(P>0.05).There are no significant differences in genotype distribution and gene frequency of that in late-onset PE groups and the control group(P > 0.05).There are no differences in genotype distribution and gene frequency of that in mild PE groups and the control group(P>0.05).There is a significant difference in genotype distribution of RBP4 gene rs3758539 locus between the severe PE case group and the control group(P <0.05),the gene frequency of that is not significant(P>0.05).2.There are no significant differences in BMI,serum ALT,AST and RBP4between women with preeclampsia compared with normal pregnant woman.The results of RT-PCR show: there is no significant change in expression of RBP4 m RNA in placenta of women with preeclampsia compared with normal pregnant woman.Conclusion:1.The rs3758539 polymorphism of RBP4 gene may be associated with preeclampsia in Shandong Han population.The rs3758539 polymorphism of RBP4 gene may be associated with early-onset preeclampsia and severe preeclampsia in Shandong Han population.2.The expression of RBP4 protein in placenta may be related to the pathogenesis of PE.