Hypomethylation of CTGF Promoter in Placenta and Peripheral Blood of Pre-eclampsia Women

Pre-eclampsia (PE) is a serious pregnancy complication defined as hypertension combined with proteinuria. Previous report has indicated that the expression of connective tissue growth factor (CTGF) is upregulated in PE placentas. In this study, we aim to investigate the potential association between the methylation of the CTGF promoter and PE. The methylation status of CTGF promoter was assessed by methylation-specific PCR and the expression of CTGF was analyzed by real-time quantitative PCR and immunohistochemistry staining, in placental samples from PE patients and normal pregnant women. The methylation level of the CTGF promoter was also analyzed in peripheral blood DNA samples from 90 PE patients and 94 normal pregnant women and further confirmed by methylation-sensitive restriction enzyme digestion combined with real-time PCR. We found a decreased methylation rate of CTGF promoter in PE placentas compared with normal control. In addition, the frequency of hemimethylated (UM) promoter of CTGF in peripheral blood was significantly lower in the PE group ( P = 0.019), while the frequency of overall methylated (MU + MM) promoter of CTGF in peripheral blood was lower (borderline significance P = 0.043) in the PE group. The percentage of methylated CpG in CTGF promoter was 30% lower in maternal blood of PE subjects than in controls. Moreover, the lower methylation frequency of CTGF promoter was in accordance with the higher expression of CTGF in trophoblast cells. Together, our data suggested an association between PE and the hypomethylation of CTGF promoter both in placentas and peripheral blood from a Chinese Han population.