| [Background]Preeclampsia(PE)is a unique and potentially life-threatening syndrome during pregnancy.Delivery of the placenta is still the only effective treatment for PE.Seeking PE treatment is of positive significance.Cyclooxygenase-2(COX-2)is a key rate-limit:ing enzyme in the enzymatic reaction of arachidonic acid into prostaglandins.COX-2 can participate in the process of in:flammation after inducing to express.Peroxisome proliferator-activated receptors-?(PPAR-?)is a ligand-activated transcription factor,which controls the transcription of genes related to metabolic function after activation.The 15-deoxy prostaglandin J2(15d-PGJ2)formed by COX-2 rate-limiting is the most important endogenous natural ligand of PPAR-y.When combined with PPAR-y,it can inhibit the activity of COX-2 through feedback,then inhibiting the expression of various inflammatory factors.Studies have shown that the combination of COX-2 inhibitors and PPAR-y agonists may be a new way to treat diseases.Based on this,the purpose of this study is to explore the relationship between COX-2 and PPAR-?(and PE,specifically from the protein and gene levels,in order to provide experimental basis for the treatment of PE.[Objective]To investigate the expression of COX-2 and PPAR-?(in plasma of PE patients and analyze their correlation,and to explore the correlation between polymorphisms and haplotypes of COX-2 and PPAR-y genes and PE in Chinese Han women,in order to provide clues for the pathogenesis and treatment of PE.[Method]1.60 cases of PE patients were selected as PE group(24 cases of mild PE group,36 cases of severe PE group)and 30 normal pregnant women who delivered at the same time as control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the protein expression levels of COX-2 and PPAR-y in the plasma of the study subjects,and to analyze the correlation between COX-2 and PPAR-y and clinical characteristics of pregnant women and pregnancy outcome.2.110 preeclampsia patients were selected as PE;group and 110 normal pregnant women as control group.COX-2 and PPAR-?(gene polymorphism in peripheral blood of pregnant women in the two groups were sequenced by SNaPshot technique.The correlation between different genotypes of each locus and PE was compared with Additive,Dominant,Recessive models.Genes haplotypes were constructed by SHEsis online software to analyze the effect of haplotypes on preeclampsia.[Result]1.Protein expression levels of COX-2 and PPAR-y1.1 COX-2:The expression levels of COX-2 in PE group were significantly higher than that in control group(P<0.05).1.2 PPAR-?(:The expression level of PPAR-y in mild PE group was significantly higher than that in control group and severe PE group(P<0.05),and the expression level of PPAR-y in control group was significantly higher than that in severe PE group(P<0.05).1.3 Correlation analysis:PPAR-y and COX-2 were positively correlated in mild PE group(r=0.414,P=0.045),and negatively correlated in severe PE group(r=-0,445,/P=0.007).2.COX-2 gene2.1 rs689466:There was no significant difference in genotype and allele frequency distribution between the two groups(P>O.05).2.2 rs20417:There was no significant difference in genotype and allele frequency distribution between the two groups(P>0.05).2.3 Single factor analysis of rs689466 and PE:Relative risk of genotype showed in Additive(AA VS AG:OR=1.618,95%CI= 0.871-3.006,P =0.158;AA VS GG:OR=1.211,95%CI=0.567-2.587,P=0.620;in Dominant(AA VS AG+GG:OR=1.484,95%CI=0.828-2.660,P=O.237);in Recessive(AA VS AG/GG:OR=0.896,95%CI=0.467-1.717,P=0.868).Relative risk of alleles showed(A VS G:OR=1.137,95%CI=0.781·1.655,P=0.503).2.4 Single factor analysis of rs20417 and PE:Relative risk of genotype was shown in Additive(CC VS CG:OR ?1.313,95%C=0.568-3.034,P=0.672);in Dominant(CC VS CG+GG:OR =1.313,95%CI=0.568-3.034,P=0.672).Relative risk of alleles was determined(C VS G:OR=1.291,95%CI=0.573-2.911,P= 0.681).2.5 Haplotype analysis:there was a strong linkage imbalance between rs689466 and rs20417(D'=0.857).There was no significant difference between monosomic C-C,C-T,G-T and PE(P>0.05).3.PPAR-y gene3.1 rs10865710:There was a critical difference in genotype frequency distribution between the two groups(P=0.050);there was a significant difference in allele frequency distribution between the two groups(P=0.015).3.2 rs3856806:There was no significant difference in genotype and allele firequency distribution between the two groups(P>0.05)·3.3 rs46847:There were significant differences in genotype and allele frequency distribution between the two groups(P=0.015O,P=0.030).3.4 Association analysis between single SNP locus and preeclampsia:The frequency of GG genotype of rs10865710 distribution in PE group was significantly higher than that in control group(OiR=2.600,95%CI:1.190-5.679,P=0.021),the frequency of alleles G in the control group was significantly lower than that of the PE group(OR=1.64,95%CI:1.117-2.411,P=0.015).The distribution frequency of CT genotype of rs4684847 in PE group was significantly higher than that in control group(OR=3.168,95%CI:l.199-8.374,P=0.026),and the frequency of T allele in PE group was significantly higher than that in control group(OR=2.987,95%CI:1.155-7.726,P-=0.030).The rs3856806 was not found to be statistically associated with the occurrence of PE.3.5 Haplotype analysis:rs10865710,rs3856806 and rs4684847 had linkage disequilibrium relationship.C-C-C haplotype was significantly correlated with PE,OR(95%CI)= 0.651(0.443-0.956),P=0.028.[Conclusion]1.The interaction between COX-2 and PPAR-y may be related to the pathogenesis of PE.2.Polymorphisms and haplotypes of rs689466 and rs20417 of COX-2 gene were not associated with genetic susceptibility to PE.3.PPAR-y gene rs10865710 polymorphism has a critical correlation with PE risk,mutant allele G may be a risk factor for PE;rs46847 polymorphism is associated with PE risk,mutant allele T may be a risk factor for PE.4.PPAR-? genes rs10865710,rs3856806 and rs4684847 have complete linkage imbalance.C-C-C haplotype may be the protective factor of PE. |
PDF Full Text Request