Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study
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 asso...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
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BioMed Central
2019
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| _version_ | 1826292202146365440 |
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| author | Mansell, T Ponsonby, A Januar, V Novakovic, B Collier, F Burgner, D Vuillermin, P Ryan, J Saffery, R Barwon Infant Study Investigator Team |
| author2 | Dwyer, T |
| author_facet | Dwyer, T Mansell, T Ponsonby, A Januar, V Novakovic, B Collier, F Burgner, D Vuillermin, P Ryan, J Saffery, R Barwon Infant Study Investigator Team |
| author_sort | Mansell, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:11:03Z |
| format | Journal article |
| id | oxford-uuid:b4370363-2cd4-4a37-9f8e-9ed4525c8c93 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:11:03Z |
| publishDate | 2019 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:b4370363-2cd4-4a37-9f8e-9ed4525c8c932022-03-27T04:24:34ZEarly-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4370363-2cd4-4a37-9f8e-9ed4525c8c93EnglishSymplectic Elements at OxfordBioMed Central2019Mansell, TPonsonby, AJanuar, VNovakovic, BCollier, FBurgner, DVuillermin, PRyan, JSaffery, RBarwon Infant Study Investigator TeamDwyer, TBACKGROUND: 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. |
| spellingShingle | Mansell, T Ponsonby, A Januar, V Novakovic, B Collier, F Burgner, D Vuillermin, P Ryan, J Saffery, R Barwon Infant Study Investigator Team Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title | Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title_full | Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title_fullStr | Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title_full_unstemmed | Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title_short | Early-life determinants of hypoxia-inducible factor 3A gene (HIF3A) methylation: a birth cohort study |
| title_sort | early life determinants of hypoxia inducible factor 3a gene hif3a methylation a birth cohort study |
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