Edematous severe acute malnutrition is characterized by hypomethylation of DNA

被引：22

作者：

Schulze, Katharina V. ^{[1
,2
]}

Swaminathan, Shanker ^{[1
,2
]}

Howell, Sharon ^{[3
]}

Jajoo, Aarti ^{[1
,2
]}

Lie, Natasha C. ^{[2
,4
]}

Brown, Orgen ^{[3
]}

Sadat, Roa ^{[2
]}

Hall, Nancy ^{[2
]}

Zhao, Liang ^{[5
]}

Marshall, Kwesi ^{[3
]}

May, Thaddaeus ^{[2
]}

Reid, Marvin E. ^{[3
]}

Taylor-Bryan, Carolyn ^{[3
]}

Wang, Xueqing ^{[1
,2
]}

Belmont, John W. ^{[1
,2
]}

Guan, Yongtao ^{[1
,2
]}

Manary, Mark J. ^{[6
,7
]}

Trehan, Indi ^{[6
,7
,8
,9
,10
]}

McKenzie, Colin A. ^{[3
]}

Hanchard, Neil A. ^{[1
,2
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, USDA, ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA

[3] Univ West Indies, Trop Metab Res Unit, Caribbean Inst Hlth Res, Mona, Jamaica

[4] Baylor Coll Med, Grad Program Integrat Mol & Biomed Sci, Houston, TX 77030 USA

[5] Taihe Hosp, Precis Med Res Ctr, Shiyan City, Peoples R China

[6] Univ Malawi, Dept Paediat & Child Hlth, Blantyre, Malawi

[7] Univ Malawi, Dept Community Hlth, Blantyre, Malawi

[8] Washington Univ, Dept Pediat, St Louis, MO 63130 USA

[9] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[10] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

EPIGENOME-WIDE ASSOCIATION; SEVERE CHILDHOOD UNDERNUTRITION; HUMAN PHENOTYPE ONTOLOGY; INSULIN-RESISTANCE; MALAWIAN CHILDREN; ADULT SURVIVORS; LOW-INCOME; METHYLATION; KWASHIORKOR; PROTEIN;

D O I：

10.1038/s41467-019-13433-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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