| [Background]Preeclampsia is the obstetric severe pregnancy complication,with prevalence of 2-8%all over the world.It can cause declined tissue perfusion of pregnant women which may induce organs injuries of pregnant women,intrauterine growth restriction of fetal and so on,being one of the major causes of maternal,fetal and neonatal death.Preeclampsia is with feature of severe illness,negative impacts on pregnancies and fetus,much complications and poor pregnancy outcomes.Nowadays,the etiology and mechanism of preeclampsia remain unknown,and there are not effective predictive methods and treatments.Therefore,identifying etiology,searching predictive biomarkers and treatment methods are becoming more important and become a hot area of researches.Pregnancy-associated plasma protein-A(PAPP-A)is a zinc-binding matrix metalloproteinase which is produced by the syncytiotrophoblast and is maintained at high concentrations in the circulation and placenta during pregnancy.Reduced PAPP-A levels have been associated both to aneuploidy and to different obstetric complications.In particular,pregnant women with reduced serum levels of PAPP-A have an increased risk of spontaneous fetal loss,preterm,intrauterine growth restriction and placental abruption.PAPP-A mediates dissociation from insulin growth factor binding proteins(IGFBPs),increasing IGF-1 bioavailablity.IGF-? could regulate and enhance trophoblast invasion by stimulation of cell migration and proliferation.Reduced PAPP-A levels may cause declined IGF-1 levels,which may cause poor trophoblast invasion.That may be one of pathogenesis of preeclampsia.Base on this,our study wants to estimate the correlation between PAPP-A and preeclampsia through two aspects,one of protein and the other of gene polymorphism.All contents of our study included three steps.Firstly,to analyze the differences of PAPP-A expression at first trimester between preeclampsia group and control group and to assess PAPP-A correlation with preeclampsia and its usefulness in predicting preeclampsia.Secondly,to analyze the differences of PAPP-A expression in patients with preeclampsia and normal control pregnancies.Lastly,to estimate whether PAPP-A polymorphism is associated with preeclampsia.Chapter One Correlation between pregnancy-associated plasma protein-A at 11?13+6 weeks of gestation and preeclampsia[Objective]To assess pregnancy-associated plasma protein A(PAPP-A)correlation with preeclampsia and its usefulness in predicting preeclampsia.[Methods]The clinical data of 48 preeclampsia patients and 50 control pregnant women undergoing antenatal examination and delivery were retrospectively analyzed from January 2015 to December 2016.The labor condition and serum PAPP-A levels of first-trimester were compared between groups.A binary Logistic regression analysis was employed to explore the risk factors of preeclampsia.The area under receiver operating characteristic(ROC-AOC)curve was used to determine the value of PAPP-A in prediction of preeclampsia.[Results]Preeclampsia and control pregnant women were significantly different in terms of age(P<0.001),BMI(P=0.003),family history of hypertension(P=0.021),gravidity(P=0.001),parity(P=0.030),gestational weeks of labor(P<0.001),way of labor(P<0.001)and weight of neonatal(P<0.001).There was no significant difference in neonatal gender between the two groups(P>0.05).Serum PAPP-A MoM values were 0.57(0.44-0.96)in women who developed preeclampsia and 0.87(0.64-1.43)in women in the control group.First trimester serum PAPP-A levels were significantly lower in women who subsequently developed preeclampsia than in women in the control group(P<0.001).Binary Logistic regression analysis revealed that PAPP-A was negatively related to the subsequently develop preeclampsia,OR 0.316(95%CI:0.117?0.854).The ROC-AUC of PAPP-A MoM was 0.717(95%CI 0.614-0.820),the adjusted score including maternal ages was 0.755(95%CI 0.659-0.851).[Conclusion]Serum PAPP-A at the first trimester of preeclampsia was lower than that of control groups.And PAPP-A was an independent influence factor in pregnant women who subsequently develop preeclampsia.It may become one of predictive values of preeclampsia.Chapeter Two Serum PAPP-A expression in patients with preeclampsia[Objective]To detect differences of serum PAPP-A expressions in patients with preeclampsia and to analyze the relationship between preeclampsia and PAPP-A expression.[Methods]From July 2014 to December 2016,132 preeclampsia patients and 158 normal pregnant women of Han nationality from the same geographic region were tested for PAPP-A genotypes.Fifty of the patients with preeclampsia and 40 of the normal pregnant women were also examined for PAPP-A expression in the serum by using enzyme-linked immunosorbent assay(ELISA)method.The discrepancy of these two biomarkers between two groups were analyzed.A binary Logistic regression was used to explore the correlation between PAPP-A and preeclampsia.[Results]Preeclampsia and control pregnant women were significantly different in terms of age(P=0.021),BMI(P=0.007),systolic pressure(P<0.001),diastolic pressure(P<0.001),way of labor(P=0.011),gestational weeks of labor(P<0.001)and weight of neonatal(P<0.001).There was no significant difference in parity between the two groups(P>0.05).Serum PAPP-A values were 12.48(11.26?14.49)mIU/L in preeclampsia women and 10.36(8.75?11.62)mIU/L in control group(P=0.003).All preeclampsia group devided into mild preeclampsia group and severe preeclampsia group for PAPP-A concentrations comparison.Serum PAPP-A values were 12.35(11.58?14.74)mIU/L in mild preeclampsia women and 12.71(10.79?14.49)mIU/L in severe preeclampsia group(P=0.705).Binary Logistic regression analysis revealed that PAPP-A was positively related to the subsequently develop preeclampsia,OR 1.892(95%CI:1.401?2.553)(P<0.001).[Conclusion]Serum PAPP-A in patients with preeclampsia was higher than that of control groups.Serum PAPP-A concentrations at second or third trimester were positively correlated with preeclampsia,which hinted PAPP-A may relate to occurrence and development of preeclampsia.Chapeter Three Correlation of PAPP-A gene polymorphism with preeclampsia[Objective]To assess correlation of PAPP-A gene rs7020782 locus and and rs12375498 locus with preeclampsia.[Methods]From July 2014 to December 2016,132 preeclampsia patients and 158 normal pregnant women of Han nationality from the same geographic region were tested for PAPP-A genotypes.By means of SNaPshot,Ser1224Tyr(rs7020782)and Cys327Cys(rs12375498)polymorphism in the PAPP-A gene were detected.The discrepancy of genotypes between these two groups were analyzed.[Results]Preeclampsia and control pregnant women were significantly different in terms of age(P=0.001),BMI(P<0.001),systolic pressure(P<0.001),diastolic pressure(P<0.001),gestational weeks of labor(P<0.001)and weight of neonatal(P<0.001).The frequency of rs7020782 locus in PAPP-A gene was in accordance with Hardy-Weinberg equilibrium,insuring the reliability of their application to evaluate groups.In preeclampsia patients,the frequencies of PAPP-A rs7020782 AA?AC and CC genotypes were 48.85%,9.16%and 34.35%,respectively,and the frequencies of PAPP-A rs7020782 A and PAPP-A rs7020782 G were 53.44%and 46.56%,respectively.The genotype frequencies of PAPP-A rs7020782 AA?AC and CC in the control group were 60.96%?8.22%? 36.67%,respectively,and the frequencies of PAPP-A rs7020782 A and PAPP-A rs7020782 G were 0.6448 and 0.3552,respectively.Codominant model revealed that the AC genotypic frequency of PAPP-A rs7020782 locus in preeclampsia group were higher than those in control group.There was no significant difference in genotype frequencies between the mild preeclampsia group and severe preeclampsia group(P>0.05).The frequency of rs12375498 locus in PAPP-A gene was not in accordance with to Hardy-Weinberg equilibrium,so later analysis was refused.[Conclusion]The AC genotype polymorphism in PAPP-A rs7020782 locus may be a risk genetic marker of preeclampsia.The frequency of rs12375498 locus in PAPP-A gene was not in accordance with to Hardy-Weinberg equilibrium,so later analysis was refused. |
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