Epigenetic changes may play an important role in the development of adult disease. Exposure to a prenatal famine environment has been associated with a persistent decrease in DNA methylation of the IGF2 gene, and other early life factors like birthweight with adult genomic DNA methylation. We evaluated genomic DNA methylation in relation to prenatal nutrition and CVD risk factors. Our study includes 353 births from three clinics with prenatal exposure to the Dutch famine of 1944–1945, 296 before-or-after the famine births as unexposed time controls, and 311 same-sex siblings of either group as unexposed family controls. All study subjects underwent medical examinations and DNA collections at a mean age of ∼58 years. We used Luminometric methylation (LUMA) and LINE-1 (Long Interspersed Nucleotide Element 1) pyrosequencing assays to quantify genomic DNA methylation. Mean DNA methylation by LUMA was 75.5% (SD 2.2) and by LINE-1 77.1% (SD 2.5). Neither was associated with prenatal famine exposure. Using all controls, famine exposure showed a decline of 0.12 % (95% CI −0.42 to 0.18; p=0.44) by LUMA and an increase of 0.05 % (−0.33 to 0.21; p=0.68) by LINE-1. Using family controls, the increases were 0.36 % (LUMA) and 0.16 % (LINE-1). Neither assay was associated with adult cholesterol, blood pressure, body size, type 2 diabetes mellitus, gender or age. Our results suggest that these genomic DNA methylation markers may not be associated with prenatal famine; further work should target regions in the genome that may be differentially methylated in response to early life exposures.
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