Promoter hypomethylation of COMT in human placenta is not associated with the development of pre-eclampsia

Abstract

Disruption of the Catechol-O-methyltransferase (COMT) gene has been shown to be involved in pre-eclampsia (PE). To investigate whether two promoters of the COMT gene are differentially regulated by methylation in PE patients, we have analyzed the genomic DNA extracted from placenta (cases n = 16; controls n = 21), maternal peripheral blood (cases n = 4; controls n = 6) and umbilical cord blood (cases n = 8; controls n = 8) of women with PE and women with normal pregnancy. Bisulfite sequencing identified the predominantly unmethylated MB-COMT promoter in placenta, maternal peripheral blood and umbilical cord blood samples (PE and control). Subsequent quantitative MassArray data confirmed a significant tissue-specific hypomethylation of the S-COMT promoter in placenta (mean = 28.6%) when compared with its densely methylated patterns in blood samples (mean = 74.5%, P < 0.001), consistent with the sequencing data. However, no PE-specific methylation difference was found between cases and controls either in placenta or in blood samples. Moreover, none of the clinical characteristics had an effect on the methylation status of the S-COMT promoter. This study does not support a causal link between methylation regulation of COMT promoters and PE. However, the observed placenta-specific S-COMT promoter may be a potential marker for early prediction of PE in maternal plasma, although this remains to be further evaluated.

Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies

“…Most have focused on specific genes (2,5–8) rather than a genome-wide approach (3,4). The changes in methylation were described in fetal-derived tissues, such as placenta, (3–5,8,17–19) or free fetal DNA in maternal plasma, (5,7) but not in maternal leukocyte DNA.…”

Normal early pregnancy

“…Most have focused on specific genes, [15][16][17][18][19] rather than a genome-wide approach, 20,21 and have concentrated on disorders of pregnancy, such as preeclampsia, 16,[19][20][21][22] intrauterine growth restriction, 17 in vitro fertilization 23 and gestational diabetes, 24 rather than normal pregnancy. 15,25 The changes in methylation have been described primarily from fetal-derived tissues, such as placenta 15,[19][20][21][23][24][25] or free fetal DNA in maternal plasma, 16,19 and only rarely in maternal DNA. 25 Our data reflect the methylation changes that occur in the DNA of white blood cells, which represent a major component of the buffy coats that were used in our experiments.…”

Up-Regulated Expression and Aberrant DNA Methylation of LEP and SH3PXD2A in Pre-Eclampsia

“…For linear correlation analysis, 12 placentas from normotensive pregnancies (5 placentas used in qRT-PCR and 7 placentas used in microarray analysis) were included. Materials of some placentas used in this study have been published in our previous study [29]. All clinical placentas from normal and pathological pregnancies were collected immediately after the caesarean section.…”