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Observational Study
. 2020 Jun;12(11):921-934.
doi: 10.2217/epi-2019-0293. Epub 2020 Jul 17.

Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases

Marion Ouidir  1 , Xuehuo Zeng  2 , Tsegaselassie Workalemahu  1 , Deepika Shrestha  1 , Katherine L Grantz  1 , Pauline Mendola  1 , Cuilin Zhang  1 , Fasil Tekola-Ayele  1
Affiliations
Observational Study

Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases

Marion Ouidir et al. Epigenomics. 2020 Jun.

Abstract

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

Keywords: cardiometabolic diseases; dyslipidemia; epigenome-wide association study; lipids; placental DNA methylation; placental gene expression.

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Conflict of interest statement

Financial & competing interests disclosure

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health including American Recovery and Reinvestment Act funding via contract numbers HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; HHSN275201000009C and HHSN27500008. Additional support was obtained from the NIH Office of the Director, the National Institute on Minority Health and Health Disparities and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Manhattan plots of associations between maternal dyslipidemia and DNA methylation in placenta.
HDLc: High-density lipoprotein cholesterol; LDLc: Low-density lipoprotein cholesterol.
See this image and copyright information in PMC

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