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Association between DNA methylation profiles in leukocytes and serum levels of persistent organic pollutants in Dutch men

ABSTRACT: Genome-wide DNA methylation profiling was performed in Dutch men consuming eel from relatively low- or high-polluted areas, resulting in a broad range of serum POP levels. The Illumina Infinium 450K Human DNA methylation Beadchip v1.0HD was used to measure DNA methylation in these men and associate this with serum levels of persistent organic pollutants (POPs). In total 48 POPs were measured, of which 30 POPs had levels above the detection limit in at least 60% of the participants. Furthermore, 11 different clinical parameters were measured as biomarkers for health. The leukocyte count was measured in each sample to adjust DNA methylation values. Furthermore, participants reported possible confounders in a questionnaire.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79329 | GEO | 2017/03/06

SECONDARY ACCESSION(S): PRJNA315514

REPOSITORIES: GEO

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Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.

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Association between DNA methylation profiles in leukocytes and serum levels of persistent organic pollutants in Dutch men

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