Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Published online

Journal Article

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.

Full Text

Cited Authors

  • Schulze, KV; Swaminathan, S; Howell, S; Jajoo, A; Lie, NC; Brown, O; Sadat, R; Hall, N; Zhao, L; Marshall, K; May, T; Reid, ME; Taylor-Bryan, C; Wang, X; Belmont, JW; Guan, Y; Manary, MJ; Trehan, I; McKenzie, CA; Hanchard, NA

Published Date

  • December 19, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 5791 -

PubMed ID

  • 31857576

Pubmed Central ID

  • 31857576

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-13433-6

Language

  • eng

Conference Location

  • England