DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study: e81731
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...
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creator | Bouwland-Both, Marieke I Mil, Nina Hvan Stolk, Lisette Eilers, Paul HC Verbiest, M PJ Heijmans, Bastiaan T Tiemeier, Henning Hofman, Albert Steegers, Eric AP Jaddoe, Vincent WV |
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 |
doi_str_mv | 10.1371/journal.pone.0081731 |
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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 ( beta = -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 ( beta = -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.</description><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081731</identifier><language>eng</language><ispartof>PloS one, 2013-12, Vol.8 (12)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,865,27929,27930</link.rule.ids></links><search><creatorcontrib>Bouwland-Both, Marieke I</creatorcontrib><creatorcontrib>Mil, Nina Hvan</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Eilers, Paul HC</creatorcontrib><creatorcontrib>Verbiest, M PJ</creatorcontrib><creatorcontrib>Heijmans, Bastiaan T</creatorcontrib><creatorcontrib>Tiemeier, Henning</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Steegers, Eric AP</creatorcontrib><creatorcontrib>Jaddoe, Vincent WV</creatorcontrib><title>DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study: e81731</title><title>PloS one</title><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 ( beta = -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 ( beta = -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.</description><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqVjsFOwkAQQDcmJqLyBx7m6IW605Wl5UbElh7wANzJhk7TkmUXO9MQ_t4E_QFP7_Ly8pR6QZ2gmeHbMQ59cD45x0CJ1hnODN6pEeYmndhUmwf1yHzUemoya0fqtPxawJqkvXonXQwQG6jKIl2uN-BCDSvMoWJYMMdD54RquHTSQkHi_E2oQuOCQNnHi7Rz2LUEJQXqf2sb2MpQX-dAt5Fndd84zzT-45N6LT53H6vJuY_fA7HsTx0fyHsXKA68x_fcZhlqOzX_UH8A0yxQ9A</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Bouwland-Both, Marieke I</creator><creator>Mil, Nina Hvan</creator><creator>Stolk, Lisette</creator><creator>Eilers, Paul HC</creator><creator>Verbiest, M PJ</creator><creator>Heijmans, Bastiaan T</creator><creator>Tiemeier, Henning</creator><creator>Hofman, Albert</creator><creator>Steegers, Eric AP</creator><creator>Jaddoe, Vincent WV</creator><scope>7TM</scope></search><sort><creationdate>20131201</creationdate><title>DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study: e81731</title><author>Bouwland-Both, Marieke I ; Mil, Nina Hvan ; Stolk, Lisette ; Eilers, Paul HC ; Verbiest, M PJ ; Heijmans, Bastiaan T ; Tiemeier, Henning ; Hofman, Albert ; Steegers, Eric AP ; Jaddoe, Vincent WV</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_14968810653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bouwland-Both, Marieke I</creatorcontrib><creatorcontrib>Mil, Nina Hvan</creatorcontrib><creatorcontrib>Stolk, Lisette</creatorcontrib><creatorcontrib>Eilers, Paul HC</creatorcontrib><creatorcontrib>Verbiest, M PJ</creatorcontrib><creatorcontrib>Heijmans, Bastiaan T</creatorcontrib><creatorcontrib>Tiemeier, Henning</creatorcontrib><creatorcontrib>Hofman, Albert</creatorcontrib><creatorcontrib>Steegers, Eric AP</creatorcontrib><creatorcontrib>Jaddoe, Vincent WV</creatorcontrib><collection>Nucleic Acids Abstracts</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bouwland-Both, Marieke I</au><au>Mil, Nina Hvan</au><au>Stolk, Lisette</au><au>Eilers, Paul HC</au><au>Verbiest, M PJ</au><au>Heijmans, Bastiaan T</au><au>Tiemeier, Henning</au><au>Hofman, Albert</au><au>Steegers, Eric AP</au><au>Jaddoe, Vincent WV</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study: e81731</atitle><jtitle>PloS one</jtitle><date>2013-12-01</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><eissn>1932-6203</eissn><abstract>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 ( beta = -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 ( beta = -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.</abstract><doi>10.1371/journal.pone.0081731</doi></addata></record> |
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title | DNA Methylation of IGF2DMR and H19 Is Associated with Fetal and Infant Growth: The Generation R Study: e81731 |
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