Early Pregnancy Dyslipidemia is Associated with Placental DNA Methylation at Loci Relevant for Cardiometabolic Diseases

Abstract

<b>Aim:</b> To identify placental DNA methylation changes that are associated with early pregnancy maternal dyslipidemia. <b>Materials & methods:</b> We analyzed placental genome-wide DNA methylation (n = 262). Genes annotating differentially methylated CpGs were evaluated for gene expression in placenta (n = 64). <b>Results:</b> We found 11 novel significant differentially methylated CpGs associated with high total cholesterol, low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol. High triglycerides were associated with decreased methylation of cg02785814 (<i>ALX4</i>) and decreased expression of <i>ALX4</i> in placenta. Genes annotating the differentially methylated CpGs play key roles in lipid metabolism and were enriched in dyslipidemia pathways. Functional annotation found <i>cis</i>-methylation quantitative trait loci for genetic loci in <i>ALX4</i> and <i>EXT2</i>. <b>Conclusion:</b> Our findings lend novel insights into potential placental epigenetic mechanisms linked with maternal dyslipidemia. <b>Trial Registration:</b> ClinicalTrials.gov, NCT00912132.