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Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk

Author

Listed:
  • Mariana L. Stevens

    (Cincinnati Children’s Hospital Medical Center)

  • Zhonghua Zhang

    (Cincinnati Children’s Hospital Medical Center)

  • Elisabet Johansson

    (Cincinnati Children’s Hospital Medical Center)

  • Samriddha Ray

    (Cincinnati Children’s Hospital Medical Center)

  • Amrita Jagpal

    (Cincinnati Children’s Hospital Medical Center)

  • Brandy P. Ruff

    (Cincinnati Children’s Hospital Medical Center)

  • Arjun Kothari

    (Cincinnati Children’s Hospital Medical Center)

  • Hua He

    (Cincinnati Children’s Hospital Medical Center)

  • Lisa J. Martin

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Hong Ji

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Kathryn Wikenheiser-Brokamp

    (University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital Medical Center)

  • Matthew T. Weirauch

    (University of Cincinnati College of Medicine
    , Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital Medical Center
    Cincinnati Children’s Hospital Medical Center)

  • Dorothy M. Supp

    (Shriners Hospitals for Children
    University of Cincinnati College of Medicine)

  • Jocelyn M. Biagini Myers

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Gurjit K. Khurana Hershey

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

Abstract

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.

Suggested Citation

  • Mariana L. Stevens & Zhonghua Zhang & Elisabet Johansson & Samriddha Ray & Amrita Jagpal & Brandy P. Ruff & Arjun Kothari & Hua He & Lisa J. Martin & Hong Ji & Kathryn Wikenheiser-Brokamp & Matthew T., 2020. "Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17895-x
    DOI: 10.1038/s41467-020-17895-x
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