Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study.
Adult
Apoptosis Regulatory Proteins
/ genetics
Birth Weight
/ genetics
Cohort Studies
CpG Islands
DNA Methylation
Diabetes, Gestational
/ epidemiology
Epigenesis, Genetic
Female
Genetic Association Studies
Gestational Age
Humans
Incidence
Infant, Newborn
Male
Pre-Eclampsia
/ epidemiology
Pregnancy
Repressor Proteins
/ genetics
DNA methylation
Gestational diabetes
HIF3A
Infant
Pre-eclampsia
Pregnancy
SNPs
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
26
11
2018
accepted:
27
05
2019
entrez:
3
7
2019
pubmed:
3
7
2019
medline:
27
5
2020
Statut:
epublish
Résumé
Methylation of the hypoxia-inducible factor 3α gene (HIF3A) has been linked to pregnancy exposures, infant adiposity and later BMI. Genetic variation influences HIF3A methylation levels and may modify these relationships. However, data in very early life are limited, particularly in association with adverse pregnancy outcomes. We investigated the relationship between maternal and gestational factors, infant anthropometry, genetic variation and HIF3A DNA methylation in the Barwon Infant Study, a population-based birth cohort. Methylation of two previously studied regions of HIF3A were tested in the cord blood mononuclear cells of 938 infants. No compelling evidence was found of an association between birth weight, adiposity or maternal gestational diabetes with methylation at the most widely studied HIF3A region. Male sex (- 4.3%, p < 0.001) and pre-eclampsia (- 5.4%, p = 0.02) negatively associated with methylation at a second region of HIF3A; while positive associations were identified for gestational diabetes (4.8%, p = 0.01) and gestational age (1.2% increase per week, p < 0.001). HIF3A genetic variation also associated strongly with methylation at this region (p < 0.001). Pre- and perinatal factors impact HIF3A methylation, including pre-eclampsia. This provides evidence that specific pregnancy complications, previously linked to adverse outcomes for both mother and child, impact the infant epigenome in a molecular pathway critical to several vascular and metabolic conditions. Further work is required to understand the mechanisms and clinical relevance, particularly the differing effects of in utero exposure to gestational diabetes or pre-eclampsia.
Sections du résumé
BACKGROUND
Methylation of the hypoxia-inducible factor 3α gene (HIF3A) has been linked to pregnancy exposures, infant adiposity and later BMI. Genetic variation influences HIF3A methylation levels and may modify these relationships. However, data in very early life are limited, particularly in association with adverse pregnancy outcomes. We investigated the relationship between maternal and gestational factors, infant anthropometry, genetic variation and HIF3A DNA methylation in the Barwon Infant Study, a population-based birth cohort. Methylation of two previously studied regions of HIF3A were tested in the cord blood mononuclear cells of 938 infants.
RESULTS
No compelling evidence was found of an association between birth weight, adiposity or maternal gestational diabetes with methylation at the most widely studied HIF3A region. Male sex (- 4.3%, p < 0.001) and pre-eclampsia (- 5.4%, p = 0.02) negatively associated with methylation at a second region of HIF3A; while positive associations were identified for gestational diabetes (4.8%, p = 0.01) and gestational age (1.2% increase per week, p < 0.001). HIF3A genetic variation also associated strongly with methylation at this region (p < 0.001).
CONCLUSIONS
Pre- and perinatal factors impact HIF3A methylation, including pre-eclampsia. This provides evidence that specific pregnancy complications, previously linked to adverse outcomes for both mother and child, impact the infant epigenome in a molecular pathway critical to several vascular and metabolic conditions. Further work is required to understand the mechanisms and clinical relevance, particularly the differing effects of in utero exposure to gestational diabetes or pre-eclampsia.
Identifiants
pubmed: 31262346
doi: 10.1186/s13148-019-0687-0
pii: 10.1186/s13148-019-0687-0
pmc: PMC6604333
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
HIF3A protein, human
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
96Investigateurs
Peter Vuillermin
(P)
Anne-Louise Ponsonby
(AL)
John Carlin
(J)
Katie Allen
(K)
Mimi Tang
(M)
Richard Saffery
(R)
Sarath Ranganathan
(S)
David Burgner
(D)
Terry Dwyer
(T)
Kim Jachno
(K)
Peter Sly
(P)
Références
Pregnancy Hypertens. 2014 Apr;4(2):97-104
pubmed: 26104417
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Hum Mol Genet. 2015 Aug 1;24(15):4464-79
pubmed: 25935004
Trends Endocrinol Metab. 2004 May-Jun;15(4):183-7
pubmed: 15109618
J Intern Med. 2007 May;261(5):412-7
pubmed: 17444880
J Clin Med Res. 2014 Feb;6(1):1-7
pubmed: 24400024
PLoS One. 2012;7(10):e46562
pubmed: 23049707
Epigenomics. 2015;7(6):937-50
pubmed: 26011824
PLoS One. 2010 Oct 12;5(10):e13288
pubmed: 20967267
Endocrinology. 2015 Oct;156(10):3422-34
pubmed: 26241064
Clin Epigenetics. 2016 Sep 02;8:89
pubmed: 27594926
Ann Hum Biol. 2011 Jan;38(1):7-11
pubmed: 21175302
PLoS One. 2015 Dec 30;10(12):e0145944
pubmed: 26717317
Diabetes. 2016 May;65(5):1231-44
pubmed: 26861784
Epigenetics. 2013 Aug;8(8):802-6
pubmed: 23811543
Int J Epidemiol. 2015 Aug;44(4):1148-60
pubmed: 25829362
Hum Mol Genet. 2015 Jul 1;24(13):3792-813
pubmed: 25861810
Psychoneuroendocrinology. 2018 Feb;88:1-8
pubmed: 29132028
Elife. 2013 Jun 04;2:e00523
pubmed: 23755361
Am J Physiol Cell Physiol. 2016 Feb 15;310(4):C260-9
pubmed: 26561641
PLoS Genet. 2011 Aug;7(8):e1002228
pubmed: 21852959
Diabetes. 2015 Sep;64(9):3146-54
pubmed: 26001398
Int J Biochem Cell Biol. 2010 Jul;42(7):1189-200
pubmed: 20416395
Clin Epigenetics. 2017 Mar 27;9:28
pubmed: 28360945
Epigenetics. 2016 Mar 3;11(3):227-36
pubmed: 26891033
Int J Epidemiol. 2015 Aug;44(4):1277-87
pubmed: 25541553
Sci Rep. 2016 Jun 27;6:27969
pubmed: 27346320
PLoS Genet. 2010 May 13;6(5):e1000952
pubmed: 20485568
Genome Biol. 2011;12(1):R10
pubmed: 21251332
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Diabetes Care. 2013 May;36(5):e64
pubmed: 23613605
J Neurosci. 2008 Sep 3;28(36):9055-65
pubmed: 18768700
Biochem Biophys Res Commun. 2007 Jan 12;352(2):437-43
pubmed: 17125738
Nat Commun. 2015 Feb 26;6:6326
pubmed: 25716334
Placenta. 2010 Mar;31 Suppl:S33-9
pubmed: 20004469
Clin Transl Immunology. 2015 Mar 27;4(3):e34
pubmed: 25859389
Br J Haematol. 2008 May;141(3):325-34
pubmed: 18410568
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Epigenomics. 2013 Feb;5(1):1-4
pubmed: 23414310
Genome Biol. 2014 May 29;15(5):R73
pubmed: 24887635
PLoS One. 2013;8(2):e55923
pubmed: 23431366
Twin Res Hum Genet. 2015 Oct;18(5):557-70
pubmed: 26337138
Acta Paediatr Suppl. 2006 Apr;450:38-46
pubmed: 16817677
Transl Psychiatry. 2016 Mar 29;6:e765
pubmed: 27023171
Gesundheitswesen. 2005 Aug;67 Suppl 1:S26-30
pubmed: 16032514
Lancet. 2014 Jun 7;383(9933):1990-8
pubmed: 24630777
PLoS Biol. 2011 Jul;9(7):e1001112
pubmed: 21814490
Oncotarget. 2017 Jun 27;8(40):67473-67481
pubmed: 28978046
Biol Pharm Bull. 2009 Jul;32(7):1166-72
pubmed: 19571379
Blood. 2009 May 21;113(21):5298-303
pubmed: 19278955
Genome Biol. 2016 Mar 31;17:61
pubmed: 27036880