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Placenta. 2014 Mar;35(3):216-22. doi: 10.1016/j.placenta.2014.01.001. Epub 2014 Jan 11.

Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia.

Author information

1
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4; Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4.
2
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
3
Department of Pathology, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
4
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4; Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4. Electronic address: wrobinson@cfri.ca.

Abstract

INTRODUCTION:

Maternal preeclampsia is associated with altered placental development in the first trimester of pregnancy. Confined placental trisomy 16 mosaicism (CPM16) is a genetic abnormality of the placenta that is highly predisposing to preeclampsia. We previously demonstrated widespread alterations in DNA methylation in 3rd trimester placentae associated with chromosomally normal early-onset preeclampsia (EOPET) and questioned whether similar changes would be associated with CPM16, making this condition a potential model for studying EOPET-associated changes early in pregnancy.

METHODS:

Using the Illumina Infinium HumanMethylation450 BeadChip, 3rd trimester CPM16 placental samples (N = 10) were compared to gestational age matched controls, and to 1st trimester trisomy 16 placentae (N = 5).

RESULTS:

DNA methylation differences associated with CPM16 were identified at 2254 CpGs using stringent criteria (FDR < 0.01, Δβ > 0.15). A subset of these differences (11%; p < 0.0001) overlapped those observed in chromosomally normal EOPET using similarly stringent criteria (FDR < 0.01; Δβ > 0.125). Importantly, the majority of EOPET-associated CpGs were significantly altered (p < 0.05) in CPM16 with a similar Δβ distribution. This was true for CPM16 with (N = 5) and without (N = 5) EOPET, although EOPET cases showed a tendency towards larger changes. Of the shared CPM16/EOPET associated changes, three CpGs near two genes (ARGHEF37 and JUNB) were also altered in 1st trimester trisomy 16 placentae.

DISCUSSION:

Despite the limited sample size, widespread DNA methylation changes are observed in Trisomy 16 that overlap those seen previously in chromosomally normal EOPET. Hence, Trisomy 16 may provide a model to study the progression of placental changes that occurs in EOPET across different gestational ages.

KEYWORDS:

450K array; DNA methylation; Placenta; Preeclampsia; Trisomy 16

PMID:
24462402
DOI:
10.1016/j.placenta.2014.01.001
[Indexed for MEDLINE]
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