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

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.