Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Autor: Schulze KV; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Swaminathan S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Howell S; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., Jajoo A; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Lie NC; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA., Brown O; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., Sadat R; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Hall N; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Zhao L; Precision Medicine Research Center, Taihe Hospital, Shiyan City, China., Marshall K; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., May T; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Reid ME; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., Taylor-Bryan C; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., Wang X; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Belmont JW; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Guan Y; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA., Manary MJ; Departments of Paediatrics and Child Health and Community Health, University of Malawi, Blantyre, Malawi.; Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA., Trehan I; Departments of Paediatrics and Child Health and Community Health, University of Malawi, Blantyre, Malawi.; Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA.; Departments of Pediatrics and Global Health, University of Washington, Seattle, WA, USA., McKenzie CA; Tropical Metabolism Research Unit, Caribbean Institute for Health Research, University of the West Indies, Mona, Jamaica., Hanchard NA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. hanchard@bcm.edu.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA. hanchard@bcm.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Dec 19; Vol. 10 (1), pp. 5791. Date of Electronic Publication: 2019 Dec 19.
DOI: 10.1038/s41467-019-13433-6
Abstrakt: 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.
Databáze: MEDLINE