Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1
Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1
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DOI：
10.3390/ijms20051066
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Sato, Noriko
中科院分区：
文献类型：
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作者：
Pavethynath, Shilpa;Imai, Chihiro;Sato, Noriko
妊娠中晚期是女性经历脂质代谢动态变化的独特时期。虽然最近密集的表观基因组关联研究（EWAS）使用外周血白细胞显示，脂质相关性状改变DNA甲基化，妊娠诱导的代谢变化对这些差异甲基化位点的甲基化水平的影响还不清楚。在这项研究中，我们使用MassARRAY EpiTYPER检测对孕妇（n = 52）进行了一项前瞻性队列研究，并分析了CPT 1A内含子1和SREBF 1内含子1 CpG的甲基化位点的甲基化水平，这些位点先前已被证实与肥胖性状密切相关。尽管SREBF 1甲基化与妊娠中期的体重指数（BMI）和低密度脂蛋白胆固醇相关，但这种相关性在妊娠晚期减弱，这与从合成代谢到分解代谢状态的代谢转换一致。然而，BMI与CPT 1A内含子1甲基化的关联似乎在妊娠晚期加强;这种关联是由妊娠中晚期白细胞比例的孕前BMI依赖性变化介导的。因此，肥胖相关的差异甲基化区域的甲基化是敏感的代谢和免疫的变化，在中期至晚期妊娠。
Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.