Nature communications · 2019
Edematous severe acute malnutrition is characterized by hypomethylation of DNA.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Schulze Katharina V, Swaminathan Shanker, Howell Sharon, Jajoo Aarti, Lie Natasha C, Brown Orgen, Sadat Roa, Hall Nancy, Zhao Liang, Marshall Kwesi, May Thaddaeus, Reid Marvin E, Taylor-Bryan Carolyn, Wang Xueqing, Belmont John W, Guan Yongtao, Manary Mark J, Trehan Indi, McKenzie Colin A, Hanchard Neil A
Аннотация
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.