title: Epigenetic signatures of gestational diabetes mellitus on cord blood methylation.
abstract: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies.
  
  
  
  Using Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes,ATP5A1,MFAP4,PRKCH, andSLC17A4, from our methylation screen and one,HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM.
  
  
  
  Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures.
authors.affiliation: Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Haertle
authors.affiliation: Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Nady
authors.initials: N
authors.lastname: El Hajj
authors.affiliation: Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.|Department of Bioinformatics, Julius Maximilians University, 97074 Würzburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dittrich
authors.affiliation: Department of Bioinformatics, Julius Maximilians University, 97074 Würzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.affiliation: Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Indrajit
authors.initials: I
authors.lastname: Nanda
authors.affiliation: Department of Gynecology and Obstetrics, Municipal Clinics, 41239 Moenchengladbach, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Lehnen
authors.affiliation: Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000097:blood* / Q000235:genetics*; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D055106:Genome-Wide Association Study; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011247:Pregnancy; D055815:Young Adult
chemical_list: D004247:DNA
keywords: DNA methylation; Fetal cord blood; Fetal programming; Gestational diabetes mellitus; Insulin treatment