HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study

Methylation levels at the hypoxia-inducible factor 3α gene (HIF3A) in blood have been linked to body mass index (BMI) in adults. Despite evidence implicating HIF3A in angiogenesis and metabolism, no studies have examined links between HIF3A methylation in early life and cardiovascular health. Here,...

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Main Authors: Toby Mansell, David Burgner, Anne-Louise Ponsonby, Fiona Collier, Angela Pezic, Peter Vuillermin, Markus Juonala, Joanne Ryan, Richard Saffery
Format: Article
Language:English
Published: Taylor & Francis Group 2020-12-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2020.1781027
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author Toby Mansell
David Burgner
Anne-Louise Ponsonby
Fiona Collier
Angela Pezic
Peter Vuillermin
Markus Juonala
Joanne Ryan
Richard Saffery
author_facet Toby Mansell
David Burgner
Anne-Louise Ponsonby
Fiona Collier
Angela Pezic
Peter Vuillermin
Markus Juonala
Joanne Ryan
Richard Saffery
author_sort Toby Mansell
collection DOAJ
description Methylation levels at the hypoxia-inducible factor 3α gene (HIF3A) in blood have been linked to body mass index (BMI) in adults. Despite evidence implicating HIF3A in angiogenesis and metabolism, no studies have examined links between HIF3A methylation in early life and cardiovascular health. Here, we investigated the relationship between HIF3A methylation in blood at birth and 12 months of age with cardiovascular measures at 4 years. We also examined influences of prenatal exposures, birth outcomes, and genetic variation. Methylation of two HIF3A promoter regions in cord blood was measured using Sequenom EpiTYPER mass-spectrometry. The first promoter region was also measured in 12-month blood. Four-year cardiovascular measures included blood pressure, pulse wave velocity, and aortic and carotid intima-media thickness. Associations were tested using partial correlation tests and linear regression modelling. Methylation of the first HIF3A promoter in cord and 12-month blood was not associated with four-year measures. There was modest evidence of an association between DNA methylation at the second HIF3A promoter in cord blood and four-year systolic blood pressure (n = 353, r = 0.12, p = 0.03). In sex-stratified analysis, methylation of the second promoter was modestly associated with systolic and diastolic blood pressure (r = 0.16, p = 0.03 for both) in males only. In conclusion, HIF3A methylation at birth shows some evidence of an association with later blood pressure in childhood. Further work should determine whether this relationship persists into later childhood, and should assess potential functional links between HIF3A methylation and cardiovascular health more generally.
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spelling doaj.art-b4e432d55484463f9f3900be838fc5da2023-09-21T13:09:23ZengTaylor & Francis GroupEpigenetics1559-22941559-23082020-12-0115121361136910.1080/15592294.2020.17810271781027HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort studyToby Mansell0David Burgner1Anne-Louise Ponsonby2Fiona Collier3Angela Pezic4Peter Vuillermin5Markus Juonala6Joanne Ryan7Richard Saffery8Murdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMurdoch Children’s Research InstituteMethylation levels at the hypoxia-inducible factor 3α gene (HIF3A) in blood have been linked to body mass index (BMI) in adults. Despite evidence implicating HIF3A in angiogenesis and metabolism, no studies have examined links between HIF3A methylation in early life and cardiovascular health. Here, we investigated the relationship between HIF3A methylation in blood at birth and 12 months of age with cardiovascular measures at 4 years. We also examined influences of prenatal exposures, birth outcomes, and genetic variation. Methylation of two HIF3A promoter regions in cord blood was measured using Sequenom EpiTYPER mass-spectrometry. The first promoter region was also measured in 12-month blood. Four-year cardiovascular measures included blood pressure, pulse wave velocity, and aortic and carotid intima-media thickness. Associations were tested using partial correlation tests and linear regression modelling. Methylation of the first HIF3A promoter in cord and 12-month blood was not associated with four-year measures. There was modest evidence of an association between DNA methylation at the second HIF3A promoter in cord blood and four-year systolic blood pressure (n = 353, r = 0.12, p = 0.03). In sex-stratified analysis, methylation of the second promoter was modestly associated with systolic and diastolic blood pressure (r = 0.16, p = 0.03 for both) in males only. In conclusion, HIF3A methylation at birth shows some evidence of an association with later blood pressure in childhood. Further work should determine whether this relationship persists into later childhood, and should assess potential functional links between HIF3A methylation and cardiovascular health more generally.http://dx.doi.org/10.1080/15592294.2020.1781027dna methylationhif3acardiovascularpaediatricscord blood
spellingShingle Toby Mansell
David Burgner
Anne-Louise Ponsonby
Fiona Collier
Angela Pezic
Peter Vuillermin
Markus Juonala
Joanne Ryan
Richard Saffery
HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
Epigenetics
dna methylation
hif3a
cardiovascular
paediatrics
cord blood
title HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
title_full HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
title_fullStr HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
title_full_unstemmed HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
title_short HIF3A cord blood methylation and systolic blood pressure at 4 years – a population-based cohort study
title_sort hif3a cord blood methylation and systolic blood pressure at 4 years a population based cohort study
topic dna methylation
hif3a
cardiovascular
paediatrics
cord blood
url http://dx.doi.org/10.1080/15592294.2020.1781027
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