TY - JOUR
T1 - Aflatoxin exposure during early life is associated with differential dna methylation in two-year-old gambian children
AU - Ghantous, Akram
AU - Novoloaca, Alexei
AU - Bouaoun, Liacine
AU - Cuenin, Cyrille
AU - Cros, Marie Pierre
AU - Xu, Ya
AU - Hernandez-Vargas, Hector
AU - Darboe, Momodou K.
AU - Prentice, Andrew M.
AU - Moore, Sophie E.
AU - Gong, Yun Yun
AU - Herceg, Zdenko
AU - Routledge, Michael N.
N1 - Funding Information:
Funding: This work was supported by the Bill and Melinda Gates Foundation (grant no: OPP1066947). The ENID trial was supported by the UK Medical Research Council (MRC) (MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/2
Y1 - 2021/8/2
N2 - Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers’ blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child’s dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
AB - Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers’ blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child’s dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.
KW - Aflatoxin albumin adducts
KW - Aflatoxin B1
KW - DNA methylation
KW - Gambian children
UR - http://www.scopus.com/inward/record.url?scp=85113780847&partnerID=8YFLogxK
U2 - 10.3390/ijms22168967
DO - 10.3390/ijms22168967
M3 - Article
AN - SCOPUS:85113780847
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 16
M1 - 8967
ER -