title: Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight.
abstract: Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns. We enrolled pregnant women in the PROGRESS birth cohort in Mexico City. Using pyrosequencing, we analyzed DNA methylation of 3 CpG sites within the AHRR gene promoter from the umbilical cord blood of 531 infants. We used generalized estimating equations to account for the correlation of DNA methylation between CpG sites. Multivariable models were used to adjust for maternal age, BMI, education, parity, smoke-exposure, infant sex, gestational age, and birth weight-for-gestational age. AHRR DNA methylation was positively associated with maternal BMI (P = 0.0009) and negatively associated with the length of gestation (P < 0.0001) and birth weight-for-gestational age (P < 0.0001). AHRR DNA methylation was 2.1% higher in offspring of obese vs. normal weight mothers and 3.1% higher in preterm vs. term infants, representing a third and a half standard deviation differences in methylation, respectively. In conclusion, offspring AHRR DNA methylation was associated with maternal obesity during pregnancy as well as infant gestational age and birth weight-for-gestational age. Further work to discover the health impacts of altered AHRR DNA methylation is warranted.
authors.affiliation: a Department of Neonatology ; Beth Israel Deaconess Medical Center and Division of Newborn Medicine; Boston Children's Hospital and Harvard Medical School ; Boston , MA USA.|b Department of Environmental Health ; Harvard School of Public Health ; Boston , MA USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Burris
authors.affiliation: b Department of Environmental Health ; Harvard School of Public Health ; Boston , MA USA.|c Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health ; Boston , MA USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: c Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health ; Boston , MA USA.|d Human Nutrition Research Center; Institute of Cellular Medicine, Newcastle University ; Newcastle upon Tyne , UK.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.affiliation: e Center for Nutrition and Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Cantoral
authors.affiliation: b Department of Environmental Health ; Harvard School of Public Health ; Boston , MA USA.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.affiliation: e Center for Nutrition and Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pantic
authors.affiliation: e Center for Nutrition and Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Maritsa
authors.initials: M
authors.lastname: Solano-Gonzalez
authors.affiliation: f Department of Pediatrics and Preventative Medicine ; Icahn School of Medicine at Mount Sinai ; New York , NY USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Svensson
authors.affiliation: e Center for Nutrition and Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Marcela
authors.initials: M
authors.lastname: Tamayo y Ortiz
authors.affiliation: c Laboratory of Environmental Epigenetics; Exposure Epidemiology and Risk Program; Harvard School of Public Health ; Boston , MA USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: f Department of Pediatrics and Preventative Medicine ; Icahn School of Medicine at Mount Sinai ; New York , NY USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.affiliation: e Center for Nutrition and Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Téllez-Rojo
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics*; D001724:Birth Weight / Q000235:genetics; D015992:Body Mass Index; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008800:Mexico; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D012097:Repressor Proteins / Q000097:blood / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; C492162:AHRR protein, human
keywords: AHRR; BMI; DNA methylation; aryl-hydrocarbon receptor repressor; epigenetics; pregnancy; preterm birth