Effect of filaggrin loss-of-function mutations on atopic dermatitis in young age: a longitudinal birth cohort study

Journal of Human Genetics volume 64, pages911–917(2019)Cite this article

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Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and skin barrier defects are often observed in patients with AD. So far, few association studies between FLG loss-of-function mutations and onset of AD in longitudinal studies of early childhood have been reported. In the present study, we aimed to investigate the effect of FLG loss-of-function mutations on the development of AD in a longitudinal birth cohort study. The status of AD diagnosis at each age until 6 years was collected from the Tokyo Children’s Health, Illness, and Development (T-CHILD) study. We analyzed eight loss-of-function mutations in FLG in 712 participants. FLG loss-of-function mutations were significantly associated with AD onset in infancy (≤2 years) (P < 0.001, OR 3.54, 95% CI 1.88–6.65), but not with AD onset in childhood (≥3 years) (P = 0.981, OR 0.99, 95% CI 0.29–3.36), and none of the children in the present cohort who developed AD at 5 years of age or later carried FLG loss-of-function mutations. Our data support the notion that the effect of FLG loss-of-function mutations is prominent during a very early stage of life.

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Acknowledgements

We thank all the participants of the T-CHILD study. We are also grateful to Flaminia Miyamasu for comments that greatly improved the manuscript and our laboratory members for useful discussions.

Funding

This work was supported by a grant from the National Center for Child Health and Development (26–18).

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Author notes

  1. These authors contributed equally: Ryota Koseki, Wataru Morii

Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Ryota Koseki, Wataru Morii, Emiko Noguchi & Moena Ishikawa

  2. Division of General Allergy, Allergy Center, National Center for Child Health and Development, Tokyo, Japan

    Limin Yang, Kiwako Yamamoto-Hanada, Masami Narita & Yukihiro Ohya

  3. National Research Institute for Child Health and Development, Tokyo, Japan

    Hirohisa Saito

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  1. Ryota Koseki
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  2. Wataru Morii
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  3. Emiko Noguchi
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  4. Moena Ishikawa
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  5. Limin Yang
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  6. Kiwako Yamamoto-Hanada
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  7. Masami Narita
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  8. Hirohisa Saito
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  9. Yukihiro Ohya
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Correspondence to Emiko Noguchi.

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Koseki, R., Morii, W., Noguchi, E. et al. Effect of filaggrin loss-of-function mutations on atopic dermatitis in young age: a longitudinal birth cohort study. J Hum Genet 64, 911–917 (2019). https://doi.org/10.1038/s10038-019-0628-y

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