Edematous severe acute malnutrition is characterized by hypomethylation of DNA

Katharina V. Schulze, Shanker Swaminathan, Sharon Howell, Aarti Jajoo, Natasha C. Lie, Orgen Brown, Roa Sadat, Nancy Hall, Liang Zhao, Kwesi Marshall, Thaddaeus May, Marvin E. Reid, Carolyn Taylor-Bryan, Xueqing Wang, John W. Belmont, Yongtao Guan, Mark J. Manary, Indi Trehan, Colin A. McKenzie and Neil A. Hanchard ()
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Katharina V. Schulze: Baylor College of Medicine
Shanker Swaminathan: Baylor College of Medicine
Sharon Howell: University of the West Indies
Aarti Jajoo: Baylor College of Medicine
Natasha C. Lie: Baylor College of Medicine
Orgen Brown: University of the West Indies
Roa Sadat: Baylor College of Medicine
Nancy Hall: Baylor College of Medicine
Liang Zhao: Taihe Hospital
Kwesi Marshall: University of the West Indies
Thaddaeus May: Baylor College of Medicine
Marvin E. Reid: University of the West Indies
Carolyn Taylor-Bryan: University of the West Indies
Xueqing Wang: Baylor College of Medicine
John W. Belmont: Baylor College of Medicine
Yongtao Guan: Baylor College of Medicine
Mark J. Manary: University of Malawi
Indi Trehan: University of Malawi
Colin A. McKenzie: University of the West Indies
Neil A. Hanchard: Baylor College of Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13433-6

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