title: Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.
abstract: BACKGROUND
  Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.
  
  
  METHODS
  We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip.
  
  
  RESULTS
  AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate < 0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-related genes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified.
  
  
  CONCLUSIONS
  This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development.
authors: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors: Hector
authors: H
authors: Hernandez-Vargas
authors: LICAMM, School of Medicine, University of Leeds, Leeds, UK.
authors: Jovita
authors: J
authors: Castelino
authors: MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
authors: Matt J
authors: MJ
authors: Silver
authors: MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
authors: Paula
authors: P
authors: Dominguez-Salas
authors: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors: Marie-Pierre
authors: MP
authors: Cros
authors: Genetic Cancer Susceptibility Group, IARC, Lyon, France.
authors: Geoffroy
authors: G
authors: Durand
authors: Genetic Cancer Susceptibility Group, IARC, Lyon, France.
authors: Florence
authors: F
authors: Le Calvez-Kelm
authors: MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
authors: Andrew M
authors: AM
authors: Prentice
authors: Director, IARC, Lyon, France.
authors: Christopher P
authors: CP
authors: Wild
authors: MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, MRC Human Nutrition Research, Cambridge, UK and.
authors: Sophie E
authors: SE
authors: Moore
authors: MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
authors: Branwen J
authors: BJ
authors: Hennig
authors: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors: Zdenko
authors: Z
authors: Herceg
authors: UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK medmnr@leeds.ac.uk.
authors: Yun Yun
authors: YY
authors: Gong
authors: LICAMM, School of Medicine, University of Leeds, Leeds, UK, medmnr@leeds.ac.uk.
authors: Michael N
authors: MN
authors: Routledge
mesh_terms: D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000097:blood*; D000348:Aflatoxins / Q000097:blood*; D000418:Albumins; D019175:DNA Methylation; D005260:Female; D005714:Gambia; D006130:Growth Disorders / Q000209:etiology; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D055815:Young Adult
chemical_list: D000348:Aflatoxins; D000418:Albumins; C098408:aflatoxin-albumin adduct; D016604:Aflatoxin B1
keywords: Aflatoxin; DNA methylation; in utero exposure