Journal Article

Edematous severe acute malnutrition is characterized by hypomethylation of DNA

Reid, Marvin E., Wang, Xueqing, Belmont, John W., Marshall, Kwesi, Taylor-Bryan, Carolyn, Jajoo, Aarti, Swaminathan, Shanker, Brown, Orgen, Manary, Mark J., Hanchard, Neil A., Hall, Nancy, Trehan, Indi, Howell, Sharon, Schulze, Katharina V., Zhao, Liang, Lie, Natasha C., Sadat, Roa, May, Thaddaeus, Guan, Yongtao, McKenzie, Colin A.

2019

Overview

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. The edematous form of severe acute childhood malnutrition (ESAM) presents with more severe multi-organ dysfunction than non-edematous SAM (NESAM). Here the authors assess genome-wide DNA methylation in buccal cells of SAM children and find that ESAM is characterized by hypomethylation at genes associated with disorders of nutrition and metabolism, including fatty liver and diabetes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/61 / 631/208/177 / 631/208/212/177 / 631/337/176/1988 / 631/443/319 / 692/699/1702/295 / Adolescent / Adult / Carbon / Case-Control Studies / Child, Preschool / Children / CpG Islands - genetics / Deoxyribonucleic acid / Diabetes mellitus / Dietary supplements / DNA / DNA Methylation / DNA microarrays / Epigenome - genetics / Epigenomics - methods / Fatty liver / Female / Gene expression / Gene Expression Profiling / Genetic diversity / Genomes / Humanities and Social Sciences / Humans / Infant / Jamaica - epidemiology / Loci / Malawi - epidemiology / Male / Malnutrition / Metabolism / Methionine / Mouth Mucosa / multidisciplinary / Nutrition / Pathogenesis / Prospective Studies / Retrospective Studies / Science / Science (multidisciplinary) / Severe Acute Malnutrition - genetics / Severe Acute Malnutrition - mortality / Survivors / Transcription / Young Adult