Aflatoxin Exposure during Early Life Is Associated with Differential DNA Methylation in Two-Year-Old Gambian Children

Abstract

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.

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood

“…Maternal BMI and plasma nutritional biomarkers including homocysteine, folate and B12 were measured on samples collected at the time of recruitment, before supplementation (median 14 weeks gestation) 21 . Blood samples and anthropometric measures including child height were obtained from a subset of ENID children aged 2 years as part of a study identifying biomarkers and understanding mechanisms for the relationship between aflatoxin exposure and child stunting 70 . DNA was extracted from white blood cells and genome-scale methylation profiles were obtained using the Illumina Human Methylation 450K Bead Chips (450K array) as described in a previous publication 71 .…”

Effects of aflatoxin and fumonisin on gene expression of growth factors and inflammation-related genes in a human hepatocyte cell line

“…Dietary exposure to aflatoxin has also been associated with child growth impairment in several epidemiology studies [ 15–19 ]. We have recently reported that dietary aflatoxin exposure is associated with differential DNA methylation in growth factor genes and immune-related genes in Gambian children, which may play a role in aflatoxin-related growth impairment [ 20 , 21 ].…”