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Dizier, Marie-Hélène; Margaritte-Jeannin, Patricia; Pain, Lucile; Sarnowski, Chloé; Brossard, Myriam; Mohamdi, Hamida; Lavielle, Nolwenn; Babron, Marie-Claude C; Just, Jocelyne; Lathrop, Mark; Laprise, Catherine; Bouzigon, Emmanuelle; Demenais, Florence; Nadif, Rachel

Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families

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  • Medientyp: E-Artikel
  • Titel: Interactive effect between ATPase-related genes and early-life tobacco smoke exposure on bronchial hyper-responsiveness detected in asthma-ascertained families
  • Beteiligte: Dizier, Marie-Hélène; Margaritte-Jeannin, Patricia; Pain, Lucile; Sarnowski, Chloé; Brossard, Myriam; Mohamdi, Hamida; Lavielle, Nolwenn; Babron, Marie-Claude C; Just, Jocelyne; Lathrop, Mark; Laprise, Catherine; Bouzigon, Emmanuelle; Demenais, Florence; Nadif, Rachel
  • Erschienen: BMJ, 2019
  • Erschienen in: Thorax
  • Sprache: Englisch
  • DOI: 10.1136/thoraxjnl-2018-211797
  • ISSN: 0040-6376; 1468-3296
  • Schlagwörter: Pulmonary and Respiratory Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>A positional cloning study of bronchial hyper-responsiveness (BHR) at the 17p11 locus in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families showed significant interaction between early-life environmental tobacco smoke (ETS) exposure and genetic variants located in <jats:italic>DNAH9</jats:italic>. This gene encodes the heavy chain subunit of axonemal dynein, which is involved with ATP in the motile cilia function.</jats:p><jats:p>Our goal was to identify genetic variants at other genes interacting with ETS in BHR by investigating all genes belonging to the ‘<jats:italic>ATP-binding</jats:italic>’ and ‘<jats:italic>ATPase activity</jats:italic>’ pathways which include <jats:italic>DNAH9,</jats:italic> are targets of cigarette smoke and play a crucial role in the airway inflammation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Family-based interaction tests between ETS-exposed and unexposed BHR siblings were conducted in 388 EGEA families. Twenty single-nucleotide polymorphisms (SNP) showing interaction signals (p<jats:italic>≤</jats:italic>5.10<jats:sup>−3</jats:sup>) were tested in the 253 Saguenay-Lac-Saint-Jean (SLSJ) families.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>One of these SNPs was significantly replicated for interaction with ETS in SLSJ families (p=0.003). Another SNP reached the significance threshold after correction for multiple testing in the combined analysis of the two samples (p=10<jats:sup>−5</jats:sup>). Results were confirmed using both a robust log-linear test and a gene-based interaction test.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The SNPs showing interaction with ETS belong to the <jats:italic>ATP8A1</jats:italic> and <jats:italic>ABCA1</jats:italic> genes, which play a role in the maintenance of asymmetry and homeostasis of lung membrane lipids.</jats:p></jats:sec>