title: Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants.
abstract: Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18-22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n = 131) and the control group (n = 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P = 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P = 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P = 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development.
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Ho-Sun
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Albino
authors.initials: A
authors.lastname: Barraza-Villarreal
authors.affiliation: Nutritional Epidemiology Group, IARC, Lyon, France;
authors.forename: Carine
authors.initials: C
authors.lastname: Biessy
authors.affiliation: Nutritional Epidemiology Group, IARC, Lyon, France;
authors.forename: Talita
authors.initials: T
authors.lastname: Duarte-Salles
authors.affiliation: Queensland Children's Medical Research Institute, Royal Children's Hospital, Herston, Queensland, Australia, and.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: Nutrition and Health Sciences and the Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Usha
authors.initials: U
authors.lastname: Ramakrishnan
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
authors.affiliation: Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México, Nutrition and Health Sciences and the Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia romieui@iarc.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000187:drug effects*; D015992:Body Mass Index; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D004281:Docosahexaenoic Acids; D007335:Insulin-Like Growth Factor II
keywords: DHA supplementation; H19; IGF2; epigenetics; imprinted genes; maternal BMI; pregnancy