Zhu Huimin, Wei Min, Liu Xuemei, Li Xiuxiu, Liu Xuhua, Chen Weiqing
Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Department of Science and Education, Shenzhen Birth Cohort Study Center, Nanshan Maternity and Child Healthcare Hospital, Shenzhen 518067, China.
Genes (Basel). 2024 Nov 25;15(12):1510. doi: 10.3390/genes15121510.
BACKGROUND/OBJECTIVES: A-kinase-interacting protein 1 (AKIP1) has been discovered to be a pivotal signaling adaptor in the regulation of human labor and associated with preterm birth, but its effect on fetal growth was still unclear. Meanwhile, the regulation role of DNA methylation (DNAm) on placental and fetal development has been demonstrated. Therefore, we aimed to investigate the association of DNAm in maternal peripheral blood with placental development and full-term small for gestational age (FT-SGA) neonates, and to explore whether placenta mediate the association between DNAm and FT-SGA; Methods: This study was a case-control study including 84 FT-SGAs and 84 FT-AGAs derived from the Shenzhen Birth Cohort Study. The DNA methylation analysis of CpG in the target region of the gene was measured by the Sequenom MassARRAY EpiTYPER approach. Multiple-variable logistic and linear regression analyses were used to estimate the association between the DNAm of three validated CpG sites in the gene, placental thickness, and FT-SGA. Mediation analysis was used to examine the mediation effect of placental development on the association between the DNAm of and FT-SGA.
For every increment in standard deviation in the DNAm of CpG4 (cg00061907) at , the risk of FT-SGA elevated by 2.01-fold (aOR = 2.01, 95%CI = 1.393.01), and the thickness of the placenta significantly decreased by a 0.19 standard deviation (β = -0.19, 95%CI = -0.32 -0.06). Placental thickness mediated the 22.96% of the effect of the DNAm of CpG4 at on the risk of FT-SGA with statistical significance.
The findings in the present study suggested the mediating effect of placental thickness on the association of the DNAm of in maternal peripheral blood and the risk of FT-SGA, providing new evidence for the mechanism of maternal epigenetics in placental and fetal development.
背景/目的：已发现A激酶相互作用蛋白1（AKIP1）是调节人类分娩的关键信号衔接蛋白，且与早产相关，但其对胎儿生长的影响仍不明确。同时，DNA甲基化（DNAm）对胎盘和胎儿发育的调节作用已得到证实。因此，我们旨在研究孕妇外周血中的DNAm与胎盘发育及足月小于胎龄（FT-SGA）新生儿之间的关联，并探讨胎盘是否介导了DNAm与FT-SGA之间的关联；方法：本研究为病例对照研究，纳入了来自深圳出生队列研究的84例FT-SGA和84例足月适于胎龄（FT-AGA）者。采用Sequenom MassARRAY EpiTYPER方法对该基因靶区域内的CpG进行DNA甲基化分析。采用多变量逻辑回归和线性回归分析来评估该基因中三个经过验证的CpG位点的DNAm、胎盘厚度与FT-SGA之间的关联。采用中介分析来检验胎盘发育对该基因的DNAm与FT-SGA之间关联的中介作用。
在该基因处，CpG4（cg00061907）的DNAm标准差每增加一个单位，FT-SGA风险升高2.01倍（调整后比值比 = 2.01，95%置信区间 = 1.393.01），胎盘厚度显著降低0.19个标准差（β = -0.19，95%置信区间 = -0.32 -0.06）。胎盘厚度介导了该基因处CpG4的DNAm对FT-SGA风险影响的22.96%，具有统计学意义。
本研究结果提示胎盘厚度对孕妇外周血中该基因的DNAm与FT-SGA风险之间的关联具有中介作用，为母体表观遗传学在胎盘和胎儿发育中的机制提供了新证据。
