title: Effects of maternal folic acid supplementation on gene methylation and being small for gestational age.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Shanghai Medical College of Fudan University, Shanghai, China.|Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Qian
authors.affiliation: Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Huang
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Liang
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: Z-F
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: J-H
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: J-P
authors.initials: JP
authors.lastname: Chen
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China. miaomaohua@163.com.
authors.forename: M-H
authors.initials: MH
authors.lastname: Miao
authors.affiliation: Key Lab. of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China. dujing42@126.com.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, CA, USA.
authors.forename: D-K
authors.initials: DK
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D019175:DNA Methylation; D019587:Dietary Supplements; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000097:blood / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D016742:Preconception Care; D011247:Pregnancy; D011295:Prenatal Care; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: C094335:H19 long non-coding RNA; D011506:Proteins; D062085:RNA, Long Noncoding; C103637:mesoderm specific transcript protein; D005492:Folic Acid
keywords: DNA methylation; birth weight; epigenetics; foetal growth; folic acid