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Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.
Hernandez-Vargas, Hector; Castelino, Jovita; Silver, Matt J; Dominguez-Salas, Paula; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Prentice, Andrew M; Wild, Christopher P; Moore, Sophie E; Hennig, Branwen J; Herceg, Zdenko; Gong, Yun Yun; Routledge, Michael N.
Afiliação
  • Hernandez-Vargas H; Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • Castelino J; LICAMM, School of Medicine, University of Leeds, Leeds, UK.
  • Silver MJ; MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
  • Dominguez-Salas P; MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
  • Cros MP; Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • Durand G; Genetic Cancer Susceptibility Group, IARC, Lyon, France.
  • Le Calvez-Kelm F; Genetic Cancer Susceptibility Group, IARC, Lyon, France.
  • Prentice AM; MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
  • Wild CP; Director, IARC, Lyon, France.
  • Moore SE; MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, MRC Human Nutrition Research, Cambridge, UK and.
  • Hennig BJ; MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia.
  • Herceg Z; Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
  • Gong YY; UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK medmnr@leeds.ac.uk.
  • Routledge MN; LICAMM, School of Medicine, University of Leeds, Leeds, UK, medmnr@leeds.ac.uk.
Int J Epidemiol ; 44(4): 1238-48, 2015 Aug.
Article em En | MEDLINE | ID: mdl-25855716
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Aflatoxina B1 / Exposição Materna / Metilação de DNA / Aflatoxinas / Leucócitos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Infant / Male / Middle aged / Pregnancy País/Região como assunto: Africa Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Aflatoxina B1 / Exposição Materna / Metilação de DNA / Aflatoxinas / Leucócitos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Female / Humans / Infant / Male / Middle aged / Pregnancy País/Região como assunto: Africa Idioma: En Ano de publicação: 2015 Tipo de documento: Article