Replicated methylation changes associated with eczema herpeticum and allergic response

Meher Preethi Boorgula, Margaret A. Taub, Nicholas Rafaels, Michelle Daya, Monica Campbell, Sameer Chavan, Aniket Shetty, Chris Cheadle, Sangjucta Barkataki, Jinshui Fan, Gloria David, Terri H. Beaty, Ingo Ruczinski, Jon Hanifin, Lynda C. Schneider, Richard L. Gallo, Amy S. Paller, Lisa A. Beck, Donald Y. Leung, Rasika A. MathiasKathleen C. Barnes

Research output: Contribution to journalArticle

Abstract

Background: Although epigenetic mechanisms are important risk factors for allergic disease, few studies have evaluated DNA methylation differences associated with atopic dermatitis (AD), and none has focused on AD with eczema herpeticum (ADEH+). We will determine how methylation varies in AD individuals with/without EH and associated traits. We modeled differences in genome-wide DNA methylation in whole blood cells from 90 ADEH+, 83 ADEH-, and 84 non-atopic, healthy control subjects, replicating in 36 ADEH+, 53 ADEH-, and 55 non-atopic healthy control subjects. We adjusted for cell-type composition in our models and used genome-wide and candidate-gene approaches. Results: We replicated one CpG which was significantly differentially methylated by severity, with suggestive replication at four others showing differential methylation by phenotype or severity. Not adjusting for eosinophil content, we identified 490 significantly differentially methylated CpGs (ADEH+ vs healthy controls, genome-wide). Many of these associated with severity measures, especially eosinophil count (431/490 sites). Conclusions: We identified a CpG in IL4 associated with serum tIgE levels, supporting a role for Th2 immune mediating mechanisms in AD. Changes in eosinophil level, a measure of disease severity, are associated with methylation changes, providing a potential mechanism for phenotypic changes in immune response-related traits.

Original languageEnglish (US)
Article number122
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
StatePublished - Aug 23 2019

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Keywords

  • Atopic dermatitis
  • DNA methylation
  • Eczema herpeticum
  • Human epigenetics
  • Infinium Methylation 450K array
  • Methylation EPIC array

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

Boorgula, M. P., Taub, M. A., Rafaels, N., Daya, M., Campbell, M., Chavan, S., Shetty, A., Cheadle, C., Barkataki, S., Fan, J., David, G., Beaty, T. H., Ruczinski, I., Hanifin, J., Schneider, L. C., Gallo, R. L., Paller, A. S., Beck, L. A., Leung, D. Y., ... Barnes, K. C. (2019). Replicated methylation changes associated with eczema herpeticum and allergic response. Clinical Epigenetics, 11(1), [122]. https://doi.org/10.1186/s13148-019-0714-1