title: Transient receptor potential genes, smoking, occupational exposures and cough in adults.
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.
authors.affiliation: INSERM, CESP Centre for research in Epidemiology and Population Health, U1018, Respiratory and environmental epidemiology Team, Villejuif F-94807, France. l.a.smit@uu.nl
authors.forename: Lidwien A M
authors.initials: LA
authors.lastname: Smit
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Josep M
authors.initials: JM
authors.lastname: Antó
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouzigon
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: González
authors.forename: Nicole
authors.initials: N
authors.lastname: Le Moual
authors.forename: Hans
authors.initials: H
authors.lastname: Kromhout
authors.forename: Anne-Elie
authors.initials: AE
authors.lastname: Carsin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pin
authors.forename: Deborah
authors.initials: D
authors.lastname: Jarvis
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.forename: Christer
authors.initials: C
authors.lastname: Janson
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Valverde
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
authors.forename: Francine
authors.initials: F
authors.lastname: Kauffmann
mesh_terms: D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics*; D016022:Case-Control Studies; D003371:Cough / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics*; D050051:Transient Receptor Potential Channels / Q000235:genetics*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C416986:TRPV4 protein, human; D050051:Transient Receptor Potential Channels