Adverse Pregnancy Outcomes, Women's Hereditary Thrombophilia Gene Polymorphism And Hemagglutination Inhibition Factor

Objective: To investigate the relationship between the 4G/5G polymorphism in the promotor region of plasminogen activator inhibitor-1(PAI -1) gene, plasma PAI-1 activity and early onset pre-eclampsia in women of Han nationality.Methods: Fifty-four patients with early onset pre-eclampsia were as study group. Sixty normal pregnancy women matched for pregnancy weeks were as control group I ,and Thirty healthy non-pregnancy women were as control group II .The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) was used to analysis 4G/5G polymorphism in the promotor region of PAI-1 gene of the leukocytes and the genotypes. The synthetic chromogenic substrate assay was used to determine plasma PAI-1 activity. The x~2 analyses were used to compare the radio of the genetypes constituent and relative risk between the study group and control group I . ANOVA was used to determine the difference of PAI-1 activity between different genotypes and between both groups. T test was used to analysis the clinical and experimental data.Results:The frequency of 4G/4G allele in the promotor region of PAI-1 gene in study group was 29.6% which was higher than that of control group I (11.7%, P=0.017), and the risk of early onset preeclampsia was increased (OR=2.540, CI=1.313~5.701). The plasma PAI-1 activity of study group women was higher significantly than that of control group-I and II(P=0.001). The plasma PAI-1 activity of different genotypes was different, from high to low arrange, 4G/4G> 4G/5G>5G/5G The physiological parameters including body mass index, edema, hematocrit, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, urine protein, placenta maturity of study group women were significantly higher than that of control group-I (P=0.001~0.037), but RBC counts,hemoglobin, albumin, fetal BPD and head .circumstance were significantly lower than that of control group I (P=0.017-0.024).Conclusion: The results suggested that there was PAI-1 gene polymorphism in women of Han nationality and 4G/4G allele homozygous genotype of PAI-1 gene may be an independent risk factor for early onset pre-eclampsia. The plasma PAI-1 activity of different genotypes from high to low were 4G/4G, 4G/5G, 5G/5G. The plasma PAI-1 activity which increased significantly after pregnancy may be one of risk factors contributing to early onset pre-eclampsia. Detection of thrombophilic mutations by molecular biological methods may be helpful to clinical diagnosis and estimation of pregnancy outcomes.Objective: To investigate the relationship between the mutation of 5, 10-methylenetetrahydrofolate reductase (MTHFR) (677 C — T, ala — val), hyperhomocysteinaemia and severe pre-eclampsia & eclampsia in women of Han nationality.Methods:Fifty-four women of severe pre-eclampsia and eclampsia and their newborns fifty cases were as study group I and study group II, respectively. Thirty health pregnant women and their newborns were as control group I and control group II, respectively.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotype in the promoter region 677situ of MTHFR. The auto fluorescence polarization-immunoassay(FPIA) was used to measure the levels of serum homocystein(Hcy). The x 2 test was used to analysis the relationship of the constituent radio of genotype, the frequency of allele gene and the risk of pre-eclampsia. One way AN OVA and T test were used to determine the difference of the genotype and serum homocystein concentration in different groups.Results: The mutation rate of the methylenetetrahydrofolate reductase gene.including homozygote T/T and heterozygote C/T, of study group I were 27.8% and 63.0% respectively, which was higher than that of the control group I (P=0.000).The mutation rate of the methylenetetrahydrofolate reductase genotypes (T/T and C/T) of study group II were 56% and 18%, respectively, which was higher than that of the control group I (P=0.000). The frequency of the T677 allele in the study group-I and II were 59.3% and 65.0%, respectively,which was higher than that of the control groups (P=0.000).The risk of severe pre-eclampsia and eclampsia of the thrmbophilia genotype T/T and C/T in both mothers and their newborns group were increased (OR=16.927, CI=5.189~ 55.221 and OR=5.692, CI=2.120—15.284, respectively), which was higher than that of control group (P=0.000).The serum homocysteine concentration of study group-I and II was significantly higher than that of control groups(P=0.000-0.007) <, The serum homocysteine concentration of different genotypes, from high to low arrange, was T/T >C/T>C/C (P=0.000~0.029). The Spearman correlation coefficient between genotypes and homocysteine concentration was -0.800~-0.844 (P=0.000).Conclusions: The results suggest that T/T homozygous genotype and C/T heterozygous of methylenetetrahydrofolate reductase(MTHFR) gene may be an independent risk factor for pre-eclampsia & eclampsia.The hyperhomocysteinaemia was also an independent risk factor for pre-eclampsia & eclampsia.So MTHFR mutation is an useful testing, it's screening by molecular biological methods is recommended. Beside this, the test of serum homocystein is also helpful for detecting the pregnancy complications.Objective: To investigate the relationship and clinical significance of the changes of anti- coagulators and placental pathology in the women with adverse pregnancy outcome.MethodsrFifty women with adverse pregnancy outcome (include early-onset preeclampsia, intrauterine growth retardation, unexplained abruptio placentae and intrauterine fetal death)were as study group. Fifty health matched for pregnancy weeks women were as control group I, and fifty healthy non-pregnancy women were as control group II .Synthetic chromogenic substrate assay or enzyme-linked immunosorbent assay(ELISA) were used to measure the plasma concentration of protein C, total protein S, antithrombin-IIIand anticardiolipin antibody. To observe the changes of the placental pathology both in the thrombophilia (anti-coagulator abnormal and anticardiolipin antibody positive) and non-thrombophilia women.ResultsrThe parameters of plasma anti-coagulator (protein C, protein S, antithrombin III) in women with adverse pregnancy outcomes were significantly lower than that of normal pregnant women, and the parameters in normal pregnant women were lower than that of healthy nonpregnant women(P<0.001~P<0.05). The deficiency rate of the prontein C, prontein S, antithrombin-III and positive rate the anticardiolipin antibody were 12%, 22%, 14% and 20% in the women with adverse pregnancy oucome, which was significantly higher than that of normal pregnancy women whose deficiency rate of the antithrombin-III was 2%, but without deficiency of prontein C, prontein S, and the anticardiolipin antibody was negative. The placental pathologic changes of women with thrombophilia(anticoagulator deficiency and anticardiolipin antibody positive) was more significant than that of non-thrombophilia women. The pathologic changes of theplacental pathology include the villous infarcts, fibrinoid necrosis of decidual vessel and small thrombosis in villous, and etc.Conclusions: The adverse pregnancy outcome was associated with thrombophilia caused by anticoagulation defect or anticardiolipin antibody positive. There are more severe vascular lesions in the placentas with thrombophilia than non- thrombophilia.The deficiency of the prontein C, prontein S, antithrombin-III deficiency and anticardiolipin antibody positive might be the early indicator of adverse pregnancy outcome.