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.

Figure 1

Forest plots of odds ratios (OR) for SNPs associated with nocturnal or usual cough in both EGEA and ECRHS, according to study and country (ECRHS). Summary ORs were calculated using a random effects meta-analysis applied to EGEA and the separate ECRHS countries. Summary ORs (95% CI) for the association between rs17706630 and rs2277675 and usual cough were 0.72 (0.57-0.91) and 0.64 (0.51-0.81), respectively. Summary ORs (95% CI) for the association between rs161365, rs17706630, rs2277675, rs150854, and rs224498 and nocturnal cough were 0.72 (0.55-0.94), 0.69 (0.54-0.88), 0.71 (0.58-0.88), 0.72 (0.56-0.92), and 1.34 (1.14-1.58), respectively. ORs for associations with usual cough could not be estimated for Switzerland, and ORs for nocturnal cough could not be estimated for the United Kingdom (UK)