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Edematous severe acute malnutrition is characterized by hypomethylation of DNA

Author

Listed:
  • Katharina V. Schulze

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Shanker Swaminathan

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Sharon Howell

    (University of the West Indies)

  • Aarti Jajoo

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Natasha C. Lie

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Orgen Brown

    (University of the West Indies)

  • Roa Sadat

    (Baylor College of Medicine)

  • Nancy Hall

    (Baylor College of Medicine)

  • Liang Zhao

    (Taihe Hospital)

  • Kwesi Marshall

    (University of the West Indies)

  • Thaddaeus May

    (Baylor College of Medicine)

  • Marvin E. Reid

    (University of the West Indies)

  • Carolyn Taylor-Bryan

    (University of the West Indies)

  • Xueqing Wang

    (Baylor College of Medicine
    Baylor College of Medicine)

  • John W. Belmont

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Yongtao Guan

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Mark J. Manary

    (University of Malawi
    Washington University in St. Louis)

  • Indi Trehan

    (University of Malawi
    Washington University in St. Louis
    University of Washington)

  • Colin A. McKenzie

    (University of the West Indies)

  • Neil A. Hanchard

    (Baylor College of Medicine
    Baylor College of Medicine)

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.

Suggested Citation

  • 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 & Caroly, 2019. "Edematous severe acute malnutrition is characterized by hypomethylation of DNA," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13433-6
    DOI: 10.1038/s41467-019-13433-6
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