Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4; Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4.
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.
Placenta. 2014 Mar;35(3):216-22. doi: 10.1016/j.placenta.2014.01.001. Epub 2014 Jan 11.
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.
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).
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.
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.
母体子痫前期与妊娠早期胎盘发育改变有关。局限性胎盘三体 16 嵌合体（CPM16）是一种胎盘的遗传异常，高度易患子痫前期。我们之前曾证明，与染色体正常的早发型子痫前期（EOPET）相关的 3 期胎盘 DNA 甲基化广泛改变，并质疑是否会与 CPM16 相关，使这种情况成为研究妊娠早期 EOPET 相关变化的潜在模型。
使用 Illumina Infinium HumanMethylation450 BeadChip，比较 3 期 CPM16 胎盘样本（N=10）与胎龄匹配的对照组，并与 1 期三体 16 胎盘（N=5）比较。
使用严格标准（FDR <0.01，Δβ>0.15）鉴定出与 CPM16 相关的 DNA 甲基化差异 2254 个 CpG。这些差异的一部分（11%；p<0.0001）与使用类似严格标准（FDR <0.01；Δβ>0.125）观察到的染色体正常的 EOPET 重叠。重要的是，大多数与 EOPET 相关的 CpG 在 CPM16 中发生了显著改变（p<0.05），其 Δβ 分布相似。对于有（N=5）和没有（N=5）EOPET 的 CPM16 均如此，尽管 EOPET 病例显示出更大变化的趋势。在 CPM16/EOPET 相关变化中，两个基因（ARGHEF37 和 JUNB）附近的三个 CpG 也在 1 期三体 16 胎盘发生改变。
尽管样本量有限，但在 Trisomy 16 中观察到广泛的 DNA 甲基化变化，与之前在染色体正常的 EOPET 中观察到的变化重叠。因此，Trisomy 16 可能为研究 EOPET 在不同胎龄时发生的胎盘变化的进展提供了一种模型。
