脐带血中免疫和脂质代谢基因的 DNA 甲基化与母亲甘油三酯和儿童肥胖有关。
Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity.
机构信息
Section of Nutrition, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
出版信息
Obesity (Silver Spring). 2024 Jan;32(1):187-199. doi: 10.1002/oby.23915. Epub 2023 Oct 23.
OBJECTIVE
Fetal exposures may impact offspring epigenetic signatures and adiposity. The authors hypothesized that maternal metabolic traits associate with cord blood DNA methylation, which, in turn, associates with child adiposity.
METHODS
Fasting serum was obtained in 588 pregnant women (27-34 weeks' gestation), and insulin, glucose, high-density lipoprotein cholesterol, triglycerides, and free fatty acids were measured. Cord blood DNA methylation and child adiposity were measured at birth, 4-6 months, and 4-6 years. The association of maternal metabolic traits with DNA methylation (429,246 CpGs) for differentially methylated probes (DMPs) and regions (DMRs) was tested. The association of the first principal component of each DMR with child adiposity was tested, and mediation analysis was performed.
RESULTS
Maternal triglycerides were associated with the most DMPs and DMRs of all traits tested (261 and 198, respectively, false discovery rate < 0.05). DMRs were near genes involved in immune function and lipid metabolism. Triglyceride-associated CpGs were associated with child adiposity at 4-6 months (32 CpGs) and 4-6 years (2 CpGs). One, near CD226, was observed at both timepoints, mediating 10% and 22% of the relationship between maternal triglycerides and child adiposity at 4-6 months and 4-6 years, respectively.
CONCLUSIONS
DNA methylation may play a role in the association of maternal triglycerides and child adiposity.
目的
胎儿暴露可能会影响后代的表观遗传特征和肥胖。作者假设，母体代谢特征与脐带血 DNA 甲基化有关，而 DNA 甲基化又与儿童肥胖有关。
方法
对 588 名孕妇（妊娠 27-34 周）进行空腹血清检测，并测量胰岛素、血糖、高密度脂蛋白胆固醇、甘油三酯和游离脂肪酸。在出生、4-6 个月和 4-6 岁时测量脐带血 DNA 甲基化和儿童肥胖。检测母体代谢特征与差异甲基化探针（DMP）和区域（DMR）的 DNA 甲基化（429,246 个 CpG）的相关性。检测每个 DMR 的第一主成分与儿童肥胖的相关性，并进行中介分析。
结果
在所有检测的特征中，母体甘油三酯与最多的 DMP 和 DMR 相关（分别为 261 和 198，假发现率<0.05）。DMR 位于参与免疫功能和脂质代谢的基因附近。与甘油三酯相关的 CpG 与 4-6 个月（32 个 CpG）和 4-6 岁（2 个 CpG）儿童肥胖相关。在这两个时间点都观察到了一个位于 CD226 附近的 CpG，它分别介导了母体甘油三酯与 4-6 个月和 4-6 岁儿童肥胖之间 10%和 22%的关系。
结论
DNA 甲基化可能在母体甘油三酯与儿童肥胖之间的关联中起作用。
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