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


CONCLUSIONS
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.
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4; Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4.
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JD
Blair
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
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Langlois
Department of Pathology, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
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DE
McFadden
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.
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Robinson
D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005865:Gestational Age; D006801:Humans; D009030:Mosaicism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D014314:Trisomy / Q000235:genetics*
450K array; DNA methylation; Placenta; Preeclampsia; Trisomy 16