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Eur Respir J. 2016 Apr;47(4):1072-81. doi: 10.1183/13993003.00849-2015. Epub 2016 Jan 21.

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

Author information

1
INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France Marie-Helene.Dizier@inserm.fr.
2
INSERM, U1168, Aging and Chronic Diseases, Epidemiological and Public Health Approaches (VIMA), Villejuif, France Université Versailles Saint-Quentin-en-Yvelines, UMR_S 1168, Paris, France These authors contributed equally to this work.
3
INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France These authors contributed equally to this work.
4
MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
5
INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France Université Paris-Sud, UMR_S 1018, Villejuif, France.
6
Université du Québec, Chicoutimi, Canada.
7
Service d'Allergologie Pédiatrique, Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand-Trousseau (APHP) - Sorbonne Universités, UPMC Université Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Paris, France.
8
McGill University and Genome Quebec's Innovation Centre, Montréal, Canada.
9
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
10
Université du Québec, Chicoutimi, Canada These authors contributed equally to this work.
11
INSERM, UMR 946, Genetic Variation and Human Diseases Unit, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.

Abstract

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.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.A single SNP reached the threshold (p≤3×10(-3)) 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.The SNP showing significant interaction with ETS belongs toDNAH9(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.

PMID:
26797031
DOI:
10.1183/13993003.00849-2015
[Indexed for MEDLINE]
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