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The Relationship of Fibrinogen and Beta-fibrinogen Gene-455G/A Polymorphism in Patients with Pre-eclampsia or Eclampsia.
Author: WangLi
Tutor: LiLi
School: Third Military Medical University
Course: Obstetrics and Gynaecology
Keywords: fibrinogen gene polymorphism pre-eclampsia/eclampsia
CLC: R714.245
Type: Master's thesis
Year: 2007
Downloads: 56
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Abstract
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Background and Objective:Pre-eclampsia/eclampsia is a unique disease to human pregnancy and the leading cause of maternal and perinatal deaths.At present,the pathogeny is still unclear,so it is difficult to prevent and cure this disease.Based on many studies,we know fibrinogen steps up abnormally in pre-eclampsia/eclampsia and blood is in hypercoagulable state or thrombotic state.It may play an important role in the pathogenesis of pre-eclampsia/ eclampsia.Beta-fibrinogen gene polymorphism is thought to be an important genetic factor which will affect concentration of fibrinogen.After research,it is found out polymorphism ofβFg-455G/A and -854G/A has separate correlation with serum fibrinogen concentration, especially the G-A replacement in -455 basic radical of upstream transcription start point ofβfibrinogen.The variance in that point may cause abnormal increase of concentration of fibrinogen.The research of gene polymorphism ofβfibrinogen -455G/A and correlation of pre-eclampsia/eclampsia is more applied in ischemic cardio-cerebrovascular disease,it is only in Jaana Laasanen’s and Raymonds’ reports and the results are negative.Because of the different distribution ofβFg-455G/A caused by country,nation and region,we presume Fg-455G/A polymorphism and pre-eclampsia/eclampsia may have area and race disparity. At present,we have not discovered any study about it in Asian.Therefore,following studies were performed:Methods and results:Section 1:Selected 20 normal non-pregnant women,respectively 52 normal pregnant women with early,middle and late pregnancy and 50 pre-eclampsia/eclampsia patients in Chongqing area.Draw fasting venous blood samples from all of them.Determine Fg,APTT, PT,TT.Apply SPSS 11.0 to make Single-factor variance analysis for each clotting indexes as well as calculation & analysis of ROC curve and area under curve(AUC).Results: compared with those of control group,the levels of Fg were obvious increased in pregnancy (P<0.01);there was no significant difference between the early and middle pregnant groups (P>0.05);but it was increased obviously in the late-pregnant(P<0.05).Additionally, fibrinogen of mild pre-eclampsia/eclampsia patients was obvious higher than that of normal late-pregnant(P<0.05).It even further increased in severe eclampsia/eclampsia(P<0.05). PT,APTT were obviously shortened only in severe eclampsia/eclampsia(P<0.05).Compared with normal late pregnant,the TT were obviously shortened in pre-eclampsia/eclampsia(P<0.05);however,there was no obvious statistic difference between mild pre-eclampsia/eclampsia and severe pre-eclampsia/eclampsia.AUC of Fg is bigger than APTT,PT,TT.At their cutoff values,both the sensitivity and specificity of Fg are better than APTT,PT,TT.Section2:Respectively selected 52 normal pregnant women with early,middle and late pregnancy and 50 pre-eclampsia/eclampsia patients in Chongqing area.Draw fasting venous blood samples from all of them.Anticoagulated by EDTA-K2,extract DNA quickly through NP40 method.AnalyzeβHaeⅢpolymorphisms(GG,GA,AA) through polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP).Results:1.Compared with normal pregnancy,genotype(GG,GA,AA) frequency and alleles(G,A) frequency of pre-eclampsia/eclampsia patients were no obviously changed(P>0.05).Besides,the difference between A gene frequency and G gene frequency has also no statistical significance(P>0.05).2.βHaeⅢpolymorphisms are significantly positive correlation with plasma fibrinogen levels(R=0.34,P<0.001).The plasma fibrinogen levels of genotypes(GA+AA) were greatly higher than group of GG.(P<0.05) 3.In pre-eclampsia/eclampsia group,both systolic pressure and diastolic pressure of the genotypes(GA+AA) were obviously higher than the genotype of GG.(P<0.05) 4.Compared with mild pre-eclampsia,severe pre-eclampsia/eclampsia have more genotypes(GA+AA) (P<0.05).Conclusions:1.As a diadynamic criteria for pre-eclampsia/eclampsia,the flexibility of Fg is 98% and the relevant specificity is 92.9%which are all higher than APTT,PT,TT.It is possibly to be a early prediction for pre-eclampsia/eclampsia. 2.Fibrinogen of pre-eclampsia/eclampsia was about one standard deviation higher than that of normal late pregnant women,which had close relation with severity degree. When the concentration of plasma fibrinogen reach to 6.84g/L,it is probably with severe pre-eclampsia/eclampsia.We guess that the rise of fibrinogen levels is an important risk factor for pre-eclampsia/eclampsia.3.AlthoughβFg-455A allele gene is not susceptibility gene of pre-eclampsia /eclampsia,it can affect concentration of plasma fibrinogen and blood pressure of preeclampsia/eclampsia. We consider thatβFg-455A allele may correlate to severity of pre-eclampsia/eclampsia.
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CLC: > Medicine, health > Obstetrics and Gynaecology > Obstetrics > Pathological pregnancy ( abnormal pregnancy ) > Gestosis > Eclampsia
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