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Transient receptor potential genes, smoking, occupational exposures and cough in adults

Lidwien AM Smit123*, Manolis Kogevinas4567, Josep M Antó4568, Emmanuelle Bouzigon10119, Juan Ramón González456, Nicole Le Moual12, Hans Kromhout3, Anne-Elie Carsin456, Isabelle Pin121314, Deborah Jarvis15, Roel Vermeulen3, Christer Janson16, Joachim Heinrich17, Ivo Gut1819, Mark Lathrop18, Miguel A Valverde20, Florence Demenais10119 and Francine Kauffmann12

Author Affiliations

1 INSERM, CESP Centre for research in Epidemiology and Population Health, U1018, Respiratory and environmental epidemiology Team, Villejuif F-94807, France

2 Université Paris Sud 11, UMRS 1018, Villejuif F-94807, France

3 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, PO Box 80178, 3508 TD Utrecht, The Netherlands

4 Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain

5 Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain

6 CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain

7 National School of Public Health, Athens, Greece

8 Department of Experimental and Health Sciences, Universitat Pompeu Fabra Barcelona, Spain

9 INSERM, U946, F-75010, Paris, France

10 Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris F-75010, France

11 Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), Paris F-75010, France

12 INSERM, U823, Grenoble, France

13 Université Joseph Fourier-Grenoble 1, Grenoble, France

14 Centre Hospitalier Universitaire de Grenoble, Grenoble, France

15 Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK

16 Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden

17 Institute of Epidemiology, Helmholtz Centre, Munich, Germany

18 Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage (CNG), Evry, France

19 Currently Centro Nacional de Analisis Genomico, Barcelona, Spain

20 Laboratory of Molecular Physiology and Channelopathies, Universitat Pompeu, Fabra, Barcelona, Spain

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Respiratory Research 2012, 13:26  doi:10.1186/1465-9921-13-26

Published: 23 March 2012

Abstract

Background

Transient receptor potential (TRP) vanilloid and ankyrin cation channels are activated by various noxious chemicals and may play an important role in the pathogenesis of cough. The aim was to study the influence of single nucleotide polymorphisms (SNPs) in TRP genes and irritant exposures on cough.

Methods

Nocturnal, usual, and chronic cough, smoking, and job history were obtained by questionnaire in 844 asthmatic and 2046 non-asthmatic adults from the Epidemiological study on the Genetics and Environment of Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Occupational exposures to vapors, gases, dusts, and/or fumes were assessed by a job-exposure matrix. Fifty-eight tagging SNPs in TRPV1, TRPV4, and TRPA1 were tested under an additive model.

Results

Statistically significant associations of 6 TRPV1 SNPs with cough symptoms were found in non-asthmatics after correction for multiple comparisons. Results were consistent across the eight countries examined. Haplotype-based association analysis confirmed the single SNP analyses for nocturnal cough (7-SNP haplotype: p-global = 4.8 × 10-6) and usual cough (9-SNP haplotype: p-global = 4.5 × 10-6). Cough symptoms were associated with exposure to irritants such as cigarette smoke and occupational exposures (p < 0.05). Four polymorphisms in TRPV1 further increased the risk of cough symptoms from irritant exposures in asthmatics and non-asthmatics (interaction p < 0.05).

Conclusions

TRPV1 SNPs were associated with cough among subjects without asthma from two independent studies in eight European countries. TRPV1 SNPs may enhance susceptibility to cough in current smokers and in subjects with a history of workplace exposures.

Keywords:
Asthma; Gene-environment interaction; Irritant exposure; Smoking; TRP channel