title: Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns.
abstract: We explored peroxisome proliferator-activated receptor-gamma co-activator 1alpha gene (PPARGC1A), peroxisome proliferator-activated receptor-gamma gene (PPARG), and transcription factor A mitochondrial gene (Tfam) promoter DNA methylation in newborns between both extremes of abnormal fetal growth: Small (SGA) and large for gestational age (LGA) in relation to the mother's characteristics. We further sought for the association of rs9930506 variant at FTO gene and the promoter patterns of DNA methylation in the aforementioned genes, in relation to the offspring's birth weight. In a cross-sectional study, 88 healthy pregnant women and their babies were included. According to the offspring birth weight, there were 57 newborns with appropriate weight for gestational age (AGA), 17 SGA, and 14 LGA. After bisulphite treatment of umbilical cord genomic DNA, a real-time methylation-specific PCR was used to determine the promoter methylation status in selected CpGs. Promoter methylated DNA/unmethylated DNA ratio, expressed as mean +/- s.e., was 0.82 +/- 0.15 (45% of alleles) for PPARGC1A, and 0.0044 +/- 0.0006 (0.4% of alleles) for Tfam. PPARG promoter was almost 100% methylated in all samples. In univariate analysis, there was no association among characteristics of the newborn and gene promoter methylation. None of the maternal features were related with the status of promoter methylation, except for a positive correlation between maternal BMI and PPARGC1A promoter methylation in umbilical cord (Pearson correlation coefficient r = 0.41, P = 0.0007). Finally, FTO rs9930506 AA homozygous in the LGA group showed decreased levels of methylated PPARGC1A in comparison with AG + GG genotypes and AGA and SGA infants. In conclusion, our findings suggest a potential role of promoter PPARGC1A methylation in metabolic programming.
authors.affiliation: Molecular Genetics and Biology of Complex Diseases Department, Institute of Medical Research, A. Lanari, University of Buenos Aires-CONICET, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gemma
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.forename: Jorge
authors.initials: J
authors.lastname: Alvariñas
authors.forename: Silvia I
authors.initials: SI
authors.lastname: García
authors.forename: Laura
authors.initials: L
authors.lastname: Quintana
authors.forename: Diego
authors.initials: D
authors.lastname: Kanevsky
authors.forename: Claudio D
authors.initials: CD
authors.lastname: González
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001724:Birth Weight; D001794:Blood Pressure; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000502:physiology; D005865:Gestational Age; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D009035:Mothers; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011506:Proteins; D014157:Transcription Factors; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human