Placental DNA methylation at term reflects maternal serum levels of INHA and FN1, but not PAPPA, early in pregnancy

BMC Medical Genetics

Research Article

Wendy P. Robinson¹  Sylvie Langlois¹  Samantha L. Wilson¹  John D. Blair²  Peter von Dadelszen³  Kirsten Hogg⁴ 

[1] Child & Family Research Institute, 950 W 28th Ave, V5Z 4H4, Vancouver, BC, Canada;Department of Medical Genetics, University of British Columbia, C201-4500 Oak St, V6H3N1, Vancouver, BC, Canada;Child & Family Research Institute, 950 W 28th Ave, V5Z 4H4, Vancouver, BC, Canada;Department of Medical Genetics, University of British Columbia, C201-4500 Oak St, V6H3N1, Vancouver, BC, Canada;Department of Molecular & Cell Biology, University of California Berkeley, Berkeley, CA, USA;Child & Family Research Institute, 950 W 28th Ave, V5Z 4H4, Vancouver, BC, Canada;Department of Obstetrics and Gynaecology, University of British Columbia, 4500 Oak St, V6H 3 V5, Vancouver, BC, Canada;Child & Family Research Institute, 950 W 28th Ave, V5Z 4H4, Vancouver, BC, Canada;Hudson Institute of Medical Research, Centre for Genetic Diseases, 27-31 Wright Street, Melbourne, Australia;

关键词: Preeclampsia;    Intrauterine growth restriction;    DNA methylation;    Maternal serum screening;    Placenta;   

DOI  :  10.1186/s12881-015-0257-z

 received in 2015-03-31, accepted in 2015-11-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundEarly detection of pregnancies at risk of complications, such as intrauterine growth restriction (IUGR) and preeclampsia (PE), is critical for improved monitoring and preventative treatment to optimize health outcomes. We predict that levels of placental-derived proteins circulating in maternal blood reflect placental gene expression, which is associated with placental DNA methylation (DNAm) profiles. As such, placental DNAm profiling may be useful to distinguish pregnancies at risk of developing complications and correlation between DNAm and protein levels in maternal blood may give further evidence for a protein’s use as a biomarker. However, few studies investigate all clinical parameters that may influence DNAm and/or protein expression, which can significantly affect the relationship between these measures.Results Candidate genes were chosen based on i) reported alterations of protein levels in maternal blood and ii) observed changes in placental DNAm (∆β > 0.05 and False Discovery Rate (FDR) <0.05) in pregnancies complicated by PE/IUGR. Fibronectin (FN1) enhancer DNAm and placental gene expression were inversely correlated (r = −0.88 p < 0.01). The same trend was observed between promoter DNAm and gene expression for INHBA and PAPPA, though not significant. INHBA and FN1 DNAm was associated with gestational–age corrected birth weight, while INHA levels were associated with fetal: placental weight ratio and FN1 level was associated with maternal body mass index (BMI).DNAm at the INHBA promoter in the term placenta was negatively correlated with second trimester maternal serum levels (r = −0.50 p = 0.01) and DNAm at the FN1 enhancer was negatively associated with third trimester maternal serum levels (r = −0.38, p = 0.009). However, a similar correlation was not found for PAPPA.ConclusionsThese results show that establishing a correlation between altered DNAm in the term placenta and altered maternal serum levels of the corresponding protein, is affected by a number of factors. Nonetheless, the correlation between placental DNAm of INHBA/FN1 and maternal serum INHA/FN1 levels indicate that DNAm may be a useful tool to identify novel biomarkers for adverse pregnancy outcomes in some cases.

【 授权许可】

CC BY   
© Wilson et al. 2015