Editors' ChoiceDiabetes

Diabetes, DNA Methylation, and in Utero Environment

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Science Translational Medicine  05 Feb 2014:
Vol. 6, Issue 222, pp. 222ec23
DOI: 10.1126/scitranslmed.3008564

Experimental animal studies are excellent for exploring the role of in utero environment. However, sooner or later, experimental findings need to be verified in humans. In a population of Pima Indians, del Rosario and coauthors analyzed whether DNA methylation is associated with diabetes in humans exposed to a diabetic intrauterine environment. This population is unusual in that they only develop type 2 diabetes, regardless of age, and prior work has shown that their risk of diabetes may be mediated by in utero exposure as well as genetics.

For this study, the authors selected nondiabetic subjects whose mothers did or did not have diabetes during pregnancy and who were a part of longitudinal community study of diabetes. Subjects were at least 50% American Indian heritage. The authors analyzed DNA from peripheral blood leukocytes and noted a tendency for global DNA hypomethylation in the offspring of diabetic mothers relative to offspring from nondiabetic mothers; 14.4% of gene regions were differentially methylated between the two groups. The researchers identified 13 pathways from the Kyoto Encyclopedia of Genes and Genomics that were enriched with differentially methylated regions. The majority of these were associated with maturity-onset diabetes of the young (MODY), type 2 diabetes, and Notch signaling. Interestingly, methylation of genes associated with obesity was not statistically different between the groups.

The authors acknowledge that analysis of leukocytes may not represent methylation patterns for all types of cells. In addition, further investigations, especially longitudinal ones, are needed to establish the exact role of epigenetic modifications in the development of diabetes in subjects exposed to a diabetic in utero environment. Nevertheless, this study demonstrates the importance of in utero exposure and provides a rationale for pursuing additional research in this area.

M. C. del Rosario et al., Potential epigenetic dysregulation of genes associated with Mody and type 2 diabetes in humans exposed to a diabetic intrauterine environment: An analysis of genome-wide DNA methylation. Metabolism, published online 21 January 2014 (10.1016/j.metabol.2014.01.007). [Full Text]

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