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Dizier, Marie-Hélène; Nadif, Rachel; Margaritte-Jeannin, Patricia; Barton, Sheila J.; Sarnowski, Chloé; Gagné-Ouellet, Valérie; Brossard, Myriam; Lavielle, Nolwenn; Just, Jocelyne; Lathrop, Mark; Holloway, John W.; Laprise, Catherine; Bouzigon, Emmanuelle; Demenais, Florence

Interaction between the DNAH9 gene and early smoke exposure in bronchial hyperresponsiveness

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  • Medientyp: E-Artikel
  • Titel: Interaction between the DNAH9 gene and early smoke exposure in bronchial hyperresponsiveness
  • Beteiligte: Dizier, Marie-Hélène; Nadif, Rachel; Margaritte-Jeannin, Patricia; Barton, Sheila J.; Sarnowski, Chloé; Gagné-Ouellet, Valérie; Brossard, Myriam; Lavielle, Nolwenn; Just, Jocelyne; Lathrop, Mark; Holloway, John W.; Laprise, Catherine; Bouzigon, Emmanuelle; Demenais, Florence
  • Erschienen: European Respiratory Society (ERS), 2016
  • Erschienen in: European Respiratory Journal
  • Sprache: Englisch
  • DOI: 10.1183/13993003.00849-2015
  • ISSN: 0903-1936; 1399-3003
  • Schlagwörter: Pulmonary and Respiratory Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>A previous genome-wide linkage scan of bronchial hyperresponsiveness (BHR) in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families, performed in the presence of a gene×early-life environmental tobacco smoke (ETS) exposure interaction, showed the strongest interaction in the 17p11 region where linkage was detected only among unexposed siblings. Our goal was to conduct fine-scale mapping of 17p11 to identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR.</jats:p><jats:p>Analyses were performed in 388 French EGEA asthmatic families, using a two-step strategy: 1) selection of SNPs displaying family-based association test (FBAT) association signals (p≤0.01) with BHR in unexposed siblings, and 2) a FBAT homogeneity test between exposed and unexposed siblings plus a robust log-linear interaction test.</jats:p><jats:p>A single SNP reached the threshold (p≤3×10<jats:sup>−3</jats:sup>) for significant interaction with ETS using both interaction tests, after accounting for multiple testing. Results were replicated in 253 French-Canadian families, but not in 341 UK families, probably due in part to differences in phenotypic features between datasets.</jats:p><jats:p>The SNP showing significant interaction with ETS belongs to <jats:italic>DNAH9</jats:italic> (dynein, axonemal, heavy chain 9), a promising candidate gene involved in respiratory cilia mobility and associated with primary ciliary dyskinesia, a disease associated with abnormalities of pulmonary function.</jats:p>
  • Zugangsstatus: Freier Zugang