Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies

Abstract

Background: Offspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity. The mechanisms behind the association of intrauterine exposure to preeclampsia and high risk of health problems in the later life remain largely unknown. The aims of the current investigation were to determine the changes in DNA methylation at IGF2 and GNAS DMR in offspring of preeclamptic pregnancy and to explore the possible mechanisms underlying the association between maternal preeclampsia and high risk for health problems in the later life of their offspring.

Results: Umbilical cord blood was taken from infants born to women of preeclampsia (n=56), gestational hypertension (n=23) and normal pregnancy (n=81). DNA methylation levels of IGF2 and GNAS DMR were determined by Massarray quantitative methylation analysis. Methylation levels at IGF2 DMR were significantly lower in preeclampsia than normal pregnancy. The average methylation level at IGF2 DMR was significantly correlated with preeclampsia even after birth weight, maternal age, gestational age at delivery and fetal gender were adjusted. The difference in methylation level was not significantly different between mild and severe preeclampsia. The methylation level at GNAS DMR was not significantly correlated with birth weight, maternal age, gestational age at delivery, fetal gender, preeclampsia or gestational hypertension.

Conclusions: We concluded preeclampsia induced a decrease in methylation level at IGF 2 DMR, and this might be among the mechanisms behind the association between intrauterine exposure to preeclampsia and high risk for metabolic diseases in the later life of the infants.

Figure 1

The comparison of Site-specific methylation levels at IGF2 DMR among normal pregnancy, gestational hypertension and preeclampsia. There were significant differences in methylation levels (Y-axle) of site 3, 6 and 7 (*: P<0.05 for all) but not the site 4, 9 and 10 among three groups (P>0.05 for all). The methylation levels of site 3, 6 and 7 were significantly lower in preeclampsia than normal pregnancy (P=0.045, 0.009, 0.048, respectively), but not significantly different between normal pregnancy and gestational hypertension, or between gestational hypertension and preeclamspsia (P>0.05 for all).

Figure 2

The comparison of Site-specific methylation levels at GNAS DMR among normal pregnancy, gestational hypertension and preeclampsia. There were no significant differences in methylation levels (Y-axle) of any site among three groups (P>0.05 for all).