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The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma

Author

Listed:
  • Rie Shigemasa
  • Hironori Masuko
  • Hisayuki Oshima
  • Kentaro Hyodo
  • Haruna Kitazawa
  • Jun Kanazawa
  • Yohei Yatagai
  • Hiroaki Iijima
  • Takashi Naito
  • Takefumi Saito
  • Satoshi Konno
  • Tomomitsu Hirota
  • Mayumi Tamari
  • Tohru Sakamoto
  • Nobuyuki Hizawa

Abstract

Background: Disturbance of mucociliary clearance is an important factor in the pathogenesis of asthma. We hypothesized that common variants in genes responsible for ciliary function may contribute to the development of asthma with certain phenotypes. Methods: Three independent adult Japanese populations (including a total of 1,158 patients with asthma and 2,203 non-asthmatic healthy participants) were studied. First, based on the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/), we selected 12 common single-nucleotide polymorphisms (SNPs) with molecular consequences (missense, nonsense, and 3’-untranslated region mutation) in 5 primary ciliary dyskinesia (PCD)-related genes and calculated a PCD-genetic risk score (GRS) as a cumulative effect of these PCD-related genes. Second, we performed a two-step cluster analysis using 3 variables, including PCD-GRS, forced expiratory volume in 1 second (%predicted FEV1), and age of asthma onset. Results: Compared to adult asthma clusters with an average PCD-GRS, clusters with high and low PCD-GRS had similar overall characteristics: adult-onset, female predominance, preserved lung function, and fewer features of type 2 immunity as determined by IgE reactivity and blood eosinophil counts. The allele frequency of rs1530496, a SNP representing an expression quantitative trait locus (eQTL) of DNAH5 in the lung, showed the largest statistically significant difference between the PCD-GRS-High and PCD-GRS-Low asthma clusters (p = 1.4 x 10−15). Conclusion: Genes associated with PCD, particularly the common SNPs associated with abnormal expression of DNAH5, may have a certain influence on the development of adult-onset asthma, perhaps through impaired mucociliary clearance.

Suggested Citation

  • Rie Shigemasa & Hironori Masuko & Hisayuki Oshima & Kentaro Hyodo & Haruna Kitazawa & Jun Kanazawa & Yohei Yatagai & Hiroaki Iijima & Takashi Naito & Takefumi Saito & Satoshi Konno & Tomomitsu Hirota , 2024. "The primary ciliary dyskinesia-related genetic risk score is associated with susceptibility to adult-onset asthma," PLOS ONE, Public Library of Science, vol. 19(3), pages 1-14, March.
    • Handle: RePEc:plo:pone00:0300000
    DOI: 10.1371/journal.pone.0300000
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    1. Miriam F. Moffatt & Michael Kabesch & Liming Liang & Anna L. Dixon & David Strachan & Simon Heath & Martin Depner & Andrea von Berg & Albrecht Bufe & Ernst Rietschel & Andrea Heinzmann & Burkard Simma, 2007. "Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma," Nature, Nature, vol. 448(7152), pages 470-473, July.
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