Abstract
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.
Highlights
Pregnancy causes extensive changes in a mother’s body to provide optimal physiological conditions for fetal growth
The association between carnitine palmitoyltransferase 1A gene (CPT1A) exon 15 methylation and body mass index (BMI) has not been identified in any epigenome-wide association studies (EWAS) reports, only Tobi et al reported its weak association with serum low-density lipoprotein cholesterol (LDL-C) level [23]
During mid-to-late gestation, maternal metabolism switches from an anabolic to a catabolic state, which is mainly characterized by an alteration in lipid metabolism
Summary
Pregnancy causes extensive changes in a mother’s body to provide optimal physiological conditions for fetal growth. The association between CPT1A exon 15 methylation and BMI has not been identified in any EWAS reports, only Tobi et al reported its weak association with serum low-density lipoprotein cholesterol (LDL-C) level [23] Since these studies have not been conducted in pregnant women, it is not known how pregnancy can influence the methylation levels of these sites. Gestational weight gain does not occur only due to an increase in fat mass [24], we mainly observed the same trend as reported in obesity-related EWAS findings at mid-gestation for the association of those methylation levels with BMI and LDL-C. Regarding the methylation level of CpG_2.3 of CPT1A exon 15, which was previously reported to be positively associated with LDL-C, no association was observed in our study (Figure S2B). Β (regression coefficient) stands for the % change in methylation per unit increase (1 kg/m2) in BMI
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