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Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years

Robert Murray, Negusse Kitaba, Elie Antoun, Philip Titcombe, Sheila Barton, Cyrus Cooper, Hazel M. Inskip, Graham C. Burdge, Pamela A. Mahon, John Deanfield, Julian Halcox Orcid Logo, Libby Ellins Orcid Logo, Jennifer Bryant, Charles Peebles, Karen Lillycrop, Keith M. Godfrey, Mark A. Hanson, (EpiGen Consortium)

Hypertension, Volume: 78, Issue: 3, Pages: 787 - 800

Swansea University Authors: Julian Halcox Orcid Logo, Libby Ellins Orcid Logo

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DOI (Published version): 10.1161/hypertensionaha.121.17396

Abstract

Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA met...

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Published in: Hypertension
ISSN: 0194-911X 1524-4563
Published: Ovid Technologies (Wolters Kluwer Health) 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa56995
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Abstract: Increases in aortic pulse wave velocity, a measure of arterial stiffness, can lead to elevated systolic blood pressure and increased cardiac afterload in adulthood. These changes are detectable in childhood and potentially originate in utero, where an adverse early life environment can alter DNA methylation patterns detectable at birth. Here, analysis of epigenome-wide methylation patterns using umbilical cord blood DNA from 470 participants in the Southampton’s Women’s Survey identified differential methylation patterns associated with systolic blood pressure, pulse pressure, arterial distensibility, and descending aorta pulse wave velocity measured by magnetic resonance imaging at 8 to 9 years. Perinatal methylation levels at 16 CpG loci were associated with descending aorta pulse wave velocity, with identified CpG sites enriched in pathways involved in DNA repair (P=9.03×10−11). The most significant association was with cg20793626 methylation (within protein phosphatase, Mg2+/Mn2+ dependent 1D; β=−0.05 m/s/1% methylation change, [95% CI, −0.09 to −0.02]). Genetic variation was also examined but had a minor influence on these observations. Eight pulse wave velocity-linked dmCpGs were associated with prenatal modifiable risk factors, with cg08509237 methylation (within palmitoyl-protein thioesterase-2) associated with maternal oily fish consumption in early and late pregnancy. Lower oily fish consumption in early pregnancy modified the relationship between methylation and pulse wave velocity, with lower consumption strengthening the association between cg08509237 methylation and increased pulse wave velocity. In conclusion, measurement of perinatal DNA methylation signatures has utility in identifying infants who might benefit from preventive interventions to reduce risk of later cardiovascular disease, and modifiable maternal factors can reduce this risk in the child.
College: Faculty of Medicine, Health and Life Sciences
Funders: This work was funded by the British Heart Foundation (RG/15/17/31749). The Southampton Women’s Survey has received funding from the Medical Research Council, Dunhill Medical Trust, British Heart Foundation, Arthritis Research UK, Food Standards Agency, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, and the European Union’s Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition, under grant agreement 289346 and the European Union’s Horizon 2020 research and innovation programme (LIFECYCLE, grant agreement No. 733206). K.M. Godfrey is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator [NF-SI-0515-10042], NIHR Southampton 1000DaysPlus Global Nutrition Research Group [17/63/154] and NIHR Southampton Biomedical Research Centre [IS-BRC-1215-20004]), and the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP).
Issue: 3
Start Page: 787
End Page: 800

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