DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study.
Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this stu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349121/pdf/?tool=EBI |
| _version_ | 1818388913416306688 |
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| author | Marieke I Bouwland-Both Nina H van Mil Lisette Stolk Paul H C Eilers Michael M P J Verbiest Bastiaan T Heijmans Henning Tiemeier Albert Hofman Eric A P Steegers Vincent W V Jaddoe Régine P M Steegers-Theunissen |
| author_facet | Marieke I Bouwland-Both Nina H van Mil Lisette Stolk Paul H C Eilers Michael M P J Verbiest Bastiaan T Heijmans Henning Tiemeier Albert Hofman Eric A P Steegers Vincent W V Jaddoe Régine P M Steegers-Theunissen |
| author_sort | Marieke I Bouwland-Both |
| collection | DOAJ |
| description | Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5-61.6) and 30.0% (25.6-34.2) and in the SGA group 52.0% (43.9-60.9) and 30.5% (23.9-32.9), respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4-4.0) and 2.4% (1.5-3.8), respectively. SGA was associated with lower IGF2DMR DNA methylation (β = -1.07, 95% CI -1.93; -0.21, P-value = 0.015), but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = -0.53, 95% CI -0.91; -0.16, P-value = 0.005). Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05), but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth. |
| first_indexed | 2024-12-14T04:33:23Z |
| format | Article |
| id | doaj.art-579738e41b814aa4963e6865f864c91b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T04:33:23Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-579738e41b814aa4963e6865f864c91b2022-12-21T23:17:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8173110.1371/journal.pone.0081731DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study.Marieke I Bouwland-BothNina H van MilLisette StolkPaul H C EilersMichael M P J VerbiestBastiaan T HeijmansHenning TiemeierAlbert HofmanEric A P SteegersVincent W V JaddoeRégine P M Steegers-TheunissenChanges in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5-61.6) and 30.0% (25.6-34.2) and in the SGA group 52.0% (43.9-60.9) and 30.5% (23.9-32.9), respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4-4.0) and 2.4% (1.5-3.8), respectively. SGA was associated with lower IGF2DMR DNA methylation (β = -1.07, 95% CI -1.93; -0.21, P-value = 0.015), but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = -0.53, 95% CI -0.91; -0.16, P-value = 0.005). Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05), but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349121/pdf/?tool=EBI |
| spellingShingle | Marieke I Bouwland-Both Nina H van Mil Lisette Stolk Paul H C Eilers Michael M P J Verbiest Bastiaan T Heijmans Henning Tiemeier Albert Hofman Eric A P Steegers Vincent W V Jaddoe Régine P M Steegers-Theunissen DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. PLoS ONE |
| title | DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. |
| title_full | DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. |
| title_fullStr | DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. |
| title_full_unstemmed | DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. |
| title_short | DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. |
| title_sort | dna methylation of igf2dmr and h19 is associated with fetal and infant growth the generation r study |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349121/pdf/?tool=EBI |
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