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; Neil A. Hanchard

doi:10.1038/s41467-019-13433-6

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, Neil A. Hanchard

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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.

Original language	English
Article number	5791
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13433-6
State	Published - Dec 1 2019

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Schulze, K. V., Swaminathan, S., Howell, S., Jajoo, A., Lie, N. C., Brown, O., Sadat, R., Hall, N., Zhao, L., Marshall, K., May, T., Reid, M. E., Taylor-Bryan, C., Wang, X., Belmont, J. W., Guan, Y., Manary, M. J., Trehan, I., McKenzie, C. A., & Hanchard, N. A. (2019). Edematous severe acute malnutrition is characterized by hypomethylation of DNA. Nature communications, 10(1), Article 5791. https://doi.org/10.1038/s41467-019-13433-6

@article{f554c465cf91490d9e28108666358734,

title = "Edematous severe acute malnutrition is characterized by hypomethylation of DNA",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13433-6",

language = "English",

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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 2019, 'Edematous severe acute malnutrition is characterized by hypomethylation of DNA', Nature communications, vol. 10, no. 1, 5791. https://doi.org/10.1038/s41467-019-13433-6

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T1 - Edematous severe acute malnutrition is characterized by hypomethylation of DNA

AU - Schulze, Katharina V.

AU - Swaminathan, Shanker

AU - Howell, Sharon

AU - Jajoo, Aarti

AU - Lie, Natasha C.

AU - Brown, Orgen

AU - Sadat, Roa

AU - Hall, Nancy

AU - Zhao, Liang

AU - Marshall, Kwesi

AU - May, Thaddaeus

AU - Reid, Marvin E.

AU - Taylor-Bryan, Carolyn

AU - Wang, Xueqing

AU - Belmont, John W.

AU - Guan, Yongtao

AU - Manary, Mark J.

AU - Trehan, Indi

AU - McKenzie, Colin A.

AU - Hanchard, Neil A.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-019-13433-6

DO - 10.1038/s41467-019-13433-6

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AN - SCOPUS:85076889324

SN - 2041-1723

VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5791

ER -

Edematous severe acute malnutrition is characterized by hypomethylation of DNA

Abstract

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