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DNA methylation at LRP1 gene locus mediates the association between maternal total cholesterol changes in pregnancy and cord blood leptin levels

Published online by Cambridge University Press:  22 November 2019

Simon-Pierre Guay ,
Andrée-Anne Houde ,
Edith Breton Open the ORCID record for Edith Breton [Opens in a new window] ,
Jean-Patrice Baillargeon ,
Patrice Perron ,
Daniel Gaudet ,
Marie-France Hivert ,
Diane Brisson  and
Luigi Bouchard
Simon-Pierre Guay
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada ECOGENE-21 Biocluster, Chicoutimi, QC, Canada Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada
Andrée-Anne Houde
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada ECOGENE-21 Biocluster, Chicoutimi, QC, Canada
Edith Breton
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada ECOGENE-21 Biocluster, Chicoutimi, QC, Canada
Jean-Patrice Baillargeon
Affiliation:
Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada
Patrice Perron
Affiliation:
ECOGENE-21 Biocluster, Chicoutimi, QC, Canada Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada
Daniel Gaudet
Affiliation:
ECOGENE-21 Biocluster, Chicoutimi, QC, Canada Department of Medicine, Université de Montréal, Montréal, QC, Canada
Marie-France Hivert
Affiliation:
Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada Department of Population Medicine, Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, MA, USA Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
Diane Brisson
Affiliation:
ECOGENE-21 Biocluster, Chicoutimi, QC, Canada Department of Medicine, Université de Montréal, Montréal, QC, Canada
Luigi Bouchard*
Affiliation:
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada ECOGENE-21 Biocluster, Chicoutimi, QC, Canada
*
Address for correspondence: Pr. Luigi Bouchard, Department of Biochemistry, Université de Sherbrooke, Chicoutimi, Québec G7H 7P2, Canada. Email: luigi.bouchard@usherbrooke.ca
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Abstract

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn’s anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns’ data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = −0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns’ cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.

Keywords

Epigeneticsfetal programminglipid metabolismCVDdyslipidemia
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 4 , August 2020 , pp. 369 - 378
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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Footnotes

†

These authors contributed equally to this work.

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