DNA methylation of APELA in preeclampsia / 中华围产医学杂志

ABSTRACT

Objective:To investigate the relationship between the methylation of apelin receptor early endogenous ligand ( APELA) gene promoter and preeclampsia. Methods:A systematic review was conducted to evaluate the cg02779075 locus methylation in APELA gene associated with preeclampsia in six previous studies on placenta genome-wide methylation based on the GEO gene expression database from 2007 to 2017. After testing the heterogeneity, the random-effects model was applied for meta-analysis. Placenta samples of 17 preeclamptic patients and 24 healthy gravidas were retrospectively collected in Obstetrics and Gynecology Hospital of Fudan University from 2008 to 2010. MassARRAY was used to quantify the methylation level of CpGs, and the expression of APELA gene was determined by qRT-PCR. All data were analyzed by t test or Mann-Whitney U test. Results:(1) Analysis of the six genome-wide methylation studies showed significant heterogeneity ( I2=0.64, P=0.016) and the meta-analysis using random-effects model showed that the methylation of cg02779075 locus in the placenta samples of preeclamptic women was down-regulated significantly ( Pmeta=6.7×10 -6). (2) Placenta tissue analysis revealed that the methylation of CpG1 [0.12 (0.00-0.25) vs 0.21 (0.09-0.33), U=-2.569] and CpG2 [0.07 (0.01-0.14) vs 0.17 (0.09-0.34), U=-4.160] in patients with preeclampsia was significantly reduced compared with those in healthy control (both P<0.05). The expression of APELA gene in the placenta was up-regulated in patients with preeclampsia, but no significant difference was observed between the two groups ( U=0.891, P=0.384). Conclusions:Aberrant methylation of APELA gene promoter was detected in the placentas of patients with preeclampsia.