Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, 90-237, Łódź, Poland.
Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Melbourne, VIC, Australia.
Sci Rep. 2022 Jan 31;12(1):1664. doi: 10.1038/s41598-022-05744-4.
Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases. The associations between maternal DNA methylation age and preeclampsia (PE) have not been fully assessed. The aim of this study was to examine if increased maternal DNA methylation age (DNAmAge) was shown to be accelerated in women with PE when compared to women who had normotensive pregnancies. The case/control cohort available for study consisted of 166 women (89 with normotensive pregnancy, 77 with PE) recruited previously at the Royal Women's Hospital in Melbourne, Australia. DNA methylation profiles were obtained using the Illumina EPIC Infinium array for analysis of genomic DNA isolated from whole blood. These profiles were used to calculate seven estimates of DNAmAge and included (1) Horvath, (2) Hannum, (3) Horvath Skin and Blood, (4) Wu, (5) PhenoAge, (6) telomere length and (7) GrimAge and its surrogate measures. Three measures of DNA methylation age acceleration were calculated for all seven measures using linear regression. Pearson's correlation was performed to investigate associations between chronological age and DNAmAge. Differences between chronological age and DNAmAge and epigenetic age acceleration were investigated using t-tests. No significant difference was observed for chronological age between women with PE (age = 30.53 ± 5.68) and women who had normotensive pregnancies (age = 31.76 ± 4.76). All seven DNAmAge measures were significantly correlated (p < 0.001) with chronological age. After accounting for multiple testing and investigating differences in DNAmAge between normotensive women and women with PE, only Wu DNAmAge was significant (p = 0.001). When examining differences for epigenetic age acceleration between PE and normotensive women Hannum, Wu, and PhenoAge DNAmAge estimates (p < 0.001) were significant for both epigenetic age acceleration and intrinsic acceleration models. We found that accelerated maternal DNAmAge is increased in women with PE in some models of epigenetic aging. This research underlines the importance for further investigation into the potential changes of differential DNA methylation in PE.
先进的生物衰老，通过 DNA 甲基化标志物评估，与多种复杂疾病有关。母体 DNA 甲基化年龄与子痫前期（PE）之间的关联尚未得到充分评估。本研究的目的是检验 PE 妇女的母体 DNA 甲基化年龄（DNAmAge）是否比正常妊娠妇女更快。本研究的病例/对照队列由 166 名女性组成（89 名正常妊娠，77 名 PE），这些女性之前在澳大利亚墨尔本的皇家妇女医院招募。使用 Illumina EPIC Infinium 阵列从全血中提取基因组 DNA 获得 DNA 甲基化谱。这些谱用于计算 7 种 DNAmAge 估计值，包括（1）Horvath，（2）Hannum，（3）Horvath 皮肤和血液，（4）Wu，（5）PhenoAge，（6）端粒长度和（7）GrimAge 及其替代测量值。使用线性回归计算所有七种方法的三种 DNA 甲基化年龄加速测量值。进行 Pearson 相关性分析以研究与实际年龄和 DNAmAge 之间的关联。使用 t 检验研究实际年龄和 DNAmAge 之间以及表观遗传年龄加速之间的差异。PE 妇女的实际年龄（年龄=30.53±5.68）与正常妊娠妇女的实际年龄（年龄=31.76±4.76）之间没有显著差异。所有七种 DNAmAge 测量值均与实际年龄显著相关（p<0.001）。在考虑到多次测试并研究正常妊娠妇女和 PE 妇女之间的 DNAmAge 差异后，只有 Wu DNAmAge 有显著差异（p=0.001）。在检查 PE 和正常妊娠妇女之间的表观遗传年龄加速差异时，Hannum、Wu 和 PhenoAge DNAmAge 估计值（p<0.001）在表观遗传年龄加速和内在加速模型中均有显著差异。我们发现，在一些表观遗传衰老模型中，PE 妇女的母体 DNAmAge 加速增加。这项研究强调了进一步研究 PE 中差异 DNA 甲基化潜在变化的重要性。
