Relationship Between DNA Methylation And RNA Expression In Promoter Region Of Coagulation Factor ? Gene And Unexplained Recurrent Abortion

Objective: 1)To investigate the distribution of(RSA)in recurrent abortion and the relationship between the number of miscarriages and the gestational age and factors of abortion;2)The relationship between recurrent abortion and coagulation indexes LA,AT ?,PT,APTT,TT,Fg,D-Dimer and PLT was analyzed;3)Relationship between DNA methylation and mRNA expression in promoter region of coagulation factor X?(FX?)gene and unexplained recurrent abortion.Methods: 1)198 patients with recurrent abortion diagnosed in the second affiliated Hospital of Xinjiang Medical University during 2018 were selected.The general data were collected,including age,frequency of abortion,gestational age of abortion,and the etiology of the patients: chromosome abnormality of husband and wife,abnormal anatomical structure of reproductive tract,abnormal endocrine system,reproductive tract infection,autoimmune abnormality and so on.According to the gestational age of abortion,the patients were divided into early RSA group(<12 weeks group)and late RSA group(?12 weeks)(43 cases),and divided into2 miscarriages group(123 cases)and?3 times according to the number of miscarriages.Group(75 cases).To analyze the etiology of RSA patients,the proportion of each factor,and the difference of RSA etiology between different abortion gestational weeks group and different abortion times group;2)198 patients with recurrent abortion treated in our hospital from January 2018 to December 2018 were selected as abortion group,198 normal pregnant women as control group 1 and 198 healthy volunteers without pregnancy as control group 2.Coagulation related indexes were detected in three groups: lupus anticoagulant factor(LA),anticoagulant ?(AT ?),prothrombin time(PT),partial activated thromboplastin time(APTT),Thrombin time(TT),Fibrinogen(Fg),D-dimer(D-Dimer)and Platelet count(PLT);3)From January 2018 to December 2018,15 patients with URSA were selected from the Department of Gynecology and Obstetrics,the secondaffiliated Hospital of Xinjiang Medical University,and 15 normal pregnant women were selected as the control group.RNA extraction,cDNA synthesis,fluorescence quantitative PCR detection and DNA extraction were performed,and(Bisulfite sequencing PCR,BSP was sequenced by bisulfite sequencing.Results: 1)The etiology of 198 patients with RSA was analyzed.There were 9 patients with chromosome abnormalities(4.55%),11 patients with abnormal anatomical structure of reproductive tract(5.56%),36 patients with abnormal endocrine system(18.18%),14 patients with reproductive tract infection(7.07%),30 patients with autoimmune abnormalities(15.15%)and 98 patients with unknown etiology(49.49%).The effect of abnormal structural anatomy of reproductive tract on patients with late RSA was greater than that of patients with early RSA(P<0.05).There was no significant difference in other causes among different gestational weeks of abortion(P>0.05).Every disease.There was no significant difference in the number of miscarriages among the groups(P>0.05);2)In abortion group,the positive rate of LA in control group 1(17.68%,10.10%)was higher than that in control group 2,the positive rate of LA in abortion group was higher than that in control group 1(P < 0.05),the expression of AT ? in abortion group was lower than that in control group 2,APTT,PT was shorter than that in control group 2,and FIB,D-Dimer was significantly higher than that in control group 2(P<0.05).Logistic regression analysis showed that LA,APTT,D-Dimer,AT ? and FIB were correlated with recurrent abortion;3)The relative expression of FX? gene mRNA in the unexplained recurrent abortion group was lower than that in the normal group(P<0.05);the methylating rate of CPG1 and CPG2 in the promoter region of FX? gene was higher than that in the case group,and the difference was statistically significant(P<0.05).Conclusions: 1)There are many factors leading to recurrent abortion,such as reproductive tract anatomy,heredity,autoimmunity,reproductive tract infection,heredity,endocrine abnormalities and unknown causes.Among them,unexplained recurrent abortion accounted for the majority.It is of great significance to understand the etiology of recurrent abortion and treat the etiology in order to improve the success rate of pregnancy and guide eugenics;2)There is a correlation between recurrent abortion and coagulation related indexes.Monitoring LA,AT ?,PT,APTT,TT,Fg,D-Dimer and PLT,provides a reference for the detection of recurrent abortion and clinical treatment;3)In this study,it was found that the expression of coagulation factor X? gene was different between the patients with unexplained recurrent abortion and the control group,and the expression of coagulation factor X? gene was significantly lower than that of the control group.The expression of FX? gene in thepromoter region of factor X? gene may be related to the increase of DNA methylation in the promoter region of factor X? gene,and the low expression of FX? gene in patients with unexplained recurrent abortion may be related to the increase of DNA methylation level in the promoter region of factor X? gene.