The Research Of Relationship Between The Estrogen And Lipid In Intrahepatic Cholestasis Of Pregnancy

Objective: To investigate estrogen change in intrahepatic cholestasis of pregnancy(ICP) and the distribution of estrogen receptorβ (ERβ) gene polymorphisms between theUygurs and the Hans in Urumqi and the association of the polymorphisms with ICP in theUygurs and the Hans. To explore the role of lipid, oxidized low-density lipoprotein(oxLDL) and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) in ICP. Toanalysis the relationship between the estrogen and lipid in ICP. Methods: The first part72patients of ICP from obstetric department of First Affiliated Hospital in XinJingMedical University were recruited from April2008to April2009and were divided intotwo groups according to the glycocholic acid (CG), severe group23cases, mild group49cases, and control group72cases. CG was analyzed by RIA, liver function and lipid weretest by enzymic mothods, Estradiol (E2), Esrtriol (E3) were analyzed by ELISA. Thesecond part The plasma oxLDL level and placenta LOX-1expression were detected in94patients (ICP group) and94healthy pregnant women (control group) from obstetricdepartment of First Affiliated Hospital in XinJing Medical University were recruited fromApril2008to September2009. The placentas LOX-1expression detected by Westernblotting; the plasma oxLDL measured by enzymelinked immunosorbent assay. The thirdpart ICP patients and controls from obstetric department of First Affiliated Hospital inXinJing Medical University were recruited from April2008to April2011, a total of105ICP patients of Uygurs as a Uygurs Case group,105ICP patients were selected by arandom number table from total Hans ICP patients as a Hans Case group,105Uygurs and105Hans healthy pregnant women were recruited as control groups. The distribution ofRsa I and Alu I of ERβ gene polymorphism were analyzed by PCR amplification andrestriction and other molecular biology approaches. Statistic analysis by χ2and Fisherexact propability. Results:1) There were significant difference among three groups aboutE2and total bile acid (TBA) and triglyeride (TG),(P＜0.01). The value of E3were nostatistics difference between severe and mild group (P＞0.05). The total bilirubin (T-BIL)and aspartate aminotransferas (AST) and alanine aminotransferase (ALT) and cholesterol (CHOL) and high density lipoprotein (HDL) and low-density lipoprotein (LDL) were nostatistics difference between control group and mild group (P＞0.05). The result of therelationship between blood-fat and estrogen and the relationship between blood-fat andliver function were analyzed by multiple factor line regression analysis, it shows that theregression equation of TG、CHOL、LDLwere statistics difference and the regressioncoefficient T-BIL is available. The coefficient of E2, CG and ALT are statisticalsignificant by multiple factor regression analysis for evaluating fetal distress.2) Theplacentas LOX-1expression in ICP group were higher than those in control group (P＜0.05), whereas the plasma oxLDL did not differ significantly between the patients withICP and healthy pregnant women (P＞0.05).3) The genotype frequency of rr、Rr、RR、aa、Aa、AA were no statistically significant between the two case groups (P＞0.05) andbetween the two control groups (P＞0.05) and between two Hans groups (P＞0.05),while it was significant different between two Uygur groups (P＜0.05). Rallelicfrequency was35.71%and50.95%in ICP patients and in control group, respectively,odds ratio (OR) was0.535[95%confidence intervals (CI)=0.3619～0.7910], P＜0.01. Aallelic frequency was21.43%and10.95%in ICP patients and in control group,respectively, OR was2.2174[95%CI=1.2866～3.8215], P＜0.05. Gene frequency ofRsaI and AluI in the two groups was distributed with polymorphism, P＜0.01. Thefrequency of RRaa in the Uygur case group was lower (4.76%,5cases) than controlgroup (13.33%,14cases)(P＜0.05), while the frequency of rrAa in the Uygur case groupwas significantly higher (14.29%,15cases) than control group (2.86%,3cases)(P＜0.05).The level of TG、CHOL、LDL、T-BIL、AST、ALT、TBA of every gene type in Uygurcase group were statistically significant, especially the lever of them in AA+Aa groupwere higher than others. Conclusions:1) E2, ALT, CHOL, LDLwere considered to be theindex of graduating the ICP, the elevated of blood-fat lever are relative to the increasingof bilirubin, it is supposed that the change of blood-fat were caused by the cholestasis, therelation between blood-fat and liver function was juxtaposed instead of causality.Blood-fat was not sensitive to predict the fetal distress, CG, E2and ALT were availableindex for evaluating fetal distress.2) LOX-1may play crucial roles in thepathophysiological processes of ICP via mediation over-apoptosis of trophoblast.Moreover, LOX-1could be a potential target for therapeutic intervention.3) Thedistribution difference of ERβgene polymorphism is no significant between the Uygursand Hans，ERβgene polymorphism may correlate with Uygurs instead of Hans, R allelemay be the guard factor, and A allele may be its risk factor．Uygurs and Hans have different genetic predisposing factors to the Development of ICP, and rrAa might be oneof risk factors for ICP in the Uygurs. ER β genetic polymorphism may control the hepaticmetabolism of pregnant women. AA+Aa genetype are factors of hepatic functiondamaged by change the encoded amino acid sequence and enhance express of estrogen βreceptors. It related to the severity of ICP.