Effects of maternal folic acid supplementation on gene methylation and being small for gestational age

Background Being small for gestational age (SGA), a foetal growth abnormality, has a long‐lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because the...

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Veröffentlicht in:Journal of human nutrition and dietetics 2016-10, Vol.29 (5), p.643-651
Hauptverfasser: Qian, Y.-Y., Huang, X.-L., Liang, H., Zhang, Z.-F., Xu, J.-H., Chen, J.-P., Yuan, W., He, L., Wang, L., Miao, M.-H., Du, J., Li, D.-K.
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container_issue 5
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container_title Journal of human nutrition and dietetics
container_volume 29
creator Qian, Y.-Y.
Huang, X.-L.
Liang, H.
Zhang, Z.-F.
Xu, J.-H.
Chen, J.-P.
Yuan, W.
He, L.
Wang, L.
Miao, M.-H.
Du, J.
Li, D.-K.
description Background Being small for gestational age (SGA), a foetal growth abnormality, has a long‐lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter‐relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. Methods We conducted a case–control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Results Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Conclusions Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri‐conception FA supplementation and also be sex‐specific.
doi_str_mv 10.1111/jhn.12369
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Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter‐relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. Methods We conducted a case–control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Results Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Conclusions Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri‐conception FA supplementation and also be sex‐specific.</description><identifier>ISSN: 0952-3871</identifier><identifier>EISSN: 1365-277X</identifier><identifier>DOI: 10.1111/jhn.12369</identifier><identifier>PMID: 27230729</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; birth weight ; Case-Control Studies ; China - epidemiology ; Cohort Studies ; Dietary Supplements ; DNA Methylation ; Epigenesis, Genetic ; epigenetics ; Female ; Fetal Blood - metabolism ; Fetal Development ; Fetal Growth Retardation - blood ; Fetal Growth Retardation - epidemiology ; Fetal Growth Retardation - metabolism ; Fetal Growth Retardation - prevention &amp; control ; foetal growth ; folic acid ; Folic Acid - therapeutic use ; Genes ; Humans ; Infant, Newborn ; Infant, Small for Gestational Age ; Male ; Maternal Nutritional Physiological Phenomena ; Preconception Care ; Pregnancy ; Prenatal Care ; Proteins - genetics ; Proteins - metabolism ; Risk Factors ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Sex Factors</subject><ispartof>Journal of human nutrition and dietetics, 2016-10, Vol.29 (5), p.643-651</ispartof><rights>2016 The British Dietetic Association Ltd.</rights><rights>2016 The British Dietetic Association Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5649-208196c61cd0e6e8c8646848635b1fc72bb2abfabb40e161131169bc07749ec33</citedby><cites>FETCH-LOGICAL-c5649-208196c61cd0e6e8c8646848635b1fc72bb2abfabb40e161131169bc07749ec33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjhn.12369$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjhn.12369$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27230729$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qian, Y.-Y.</creatorcontrib><creatorcontrib>Huang, X.-L.</creatorcontrib><creatorcontrib>Liang, H.</creatorcontrib><creatorcontrib>Zhang, Z.-F.</creatorcontrib><creatorcontrib>Xu, J.-H.</creatorcontrib><creatorcontrib>Chen, J.-P.</creatorcontrib><creatorcontrib>Yuan, W.</creatorcontrib><creatorcontrib>He, L.</creatorcontrib><creatorcontrib>Wang, L.</creatorcontrib><creatorcontrib>Miao, M.-H.</creatorcontrib><creatorcontrib>Du, J.</creatorcontrib><creatorcontrib>Li, D.-K.</creatorcontrib><title>Effects of maternal folic acid supplementation on gene methylation and being small for gestational age</title><title>Journal of human nutrition and dietetics</title><addtitle>J Hum Nutr Diet</addtitle><description>Background Being small for gestational age (SGA), a foetal growth abnormality, has a long‐lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter‐relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. Methods We conducted a case–control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Results Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Conclusions Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. 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Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Journal of human nutrition and dietetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qian, Y.-Y.</au><au>Huang, X.-L.</au><au>Liang, H.</au><au>Zhang, Z.-F.</au><au>Xu, J.-H.</au><au>Chen, J.-P.</au><au>Yuan, W.</au><au>He, L.</au><au>Wang, L.</au><au>Miao, M.-H.</au><au>Du, J.</au><au>Li, D.-K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of maternal folic acid supplementation on gene methylation and being small for gestational age</atitle><jtitle>Journal of human nutrition and dietetics</jtitle><addtitle>J Hum Nutr Diet</addtitle><date>2016-10</date><risdate>2016</risdate><volume>29</volume><issue>5</issue><spage>643</spage><epage>651</epage><pages>643-651</pages><issn>0952-3871</issn><eissn>1365-277X</eissn><abstract>Background Being small for gestational age (SGA), a foetal growth abnormality, has a long‐lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter‐relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. Methods We conducted a case–control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. Results Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). Conclusions Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri‐conception FA supplementation and also be sex‐specific.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27230729</pmid><doi>10.1111/jhn.12369</doi><tpages>9</tpages></addata></record>
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subjects Adult
birth weight
Case-Control Studies
China - epidemiology
Cohort Studies
Dietary Supplements
DNA Methylation
Epigenesis, Genetic
epigenetics
Female
Fetal Blood - metabolism
Fetal Development
Fetal Growth Retardation - blood
Fetal Growth Retardation - epidemiology
Fetal Growth Retardation - metabolism
Fetal Growth Retardation - prevention & control
foetal growth
folic acid
Folic Acid - therapeutic use
Genes
Humans
Infant, Newborn
Infant, Small for Gestational Age
Male
Maternal Nutritional Physiological Phenomena
Preconception Care
Pregnancy
Prenatal Care
Proteins - genetics
Proteins - metabolism
Risk Factors
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Sex Factors
title Effects of maternal folic acid supplementation on gene methylation and being small for gestational age
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