M12TRPV1 polymorphism in chronic cough: no evidence for an effect on objective measurements of cough

• Published in: Thorax Vol. 71; no. Suppl 3; p. A263
• Main Authors: Turner, R D, Bourne, E, Mein, CA, Birring, S S, Shaheen, SO, Bothamley, G H
• Format: Journal Article
• Language: English
• Published: 01.12.2016
• ISSN: 0040-6376
• DOI: 10.1136/thoraxjnl-2016-209333.454

Introduction and objectivesThe afferent receptor TRPV1 is implicated in the cough reflex. Several single nucleotide polymorphisms (SNPs) in TRPV1 appear to be associated with symptoms of cough in the general population.1 We investigated whether such SNPs are associated with the objective measures of cough reflex sensitivity and 24-hour cough frequency (CF24) in chronic cough.MethodsPatients were recruited from a specialist cough clinic with cough >2 months' duration as the only or predominant symptom. Each underwent measurement of C5 (minimum concentration of capsaicin required to produce 5 coughs) and wore the Leicester Cough Monitor for 24 h. Saliva samples were taken to extract DNA and genotype six SNPs of TRPV1: rs161365, rs17706630, rs2277675, rs222741, rs150854 and rs224498. Mean values of C5 and CF24 were compared across genotypes and univariate linear regression was used to analyse the per minor allele associations with each outcome for each SNP, on the assumption their effects would be additive.1 Results57 patients were recruited with underlying diagnoses including unexplained chronic cough (n = 43), asthma (n = 7) and gastro-oesophageal reflux (n = 2). 42 (74%) were female, and median (IQR) age and duration of cough was 60 (54-66) years and 5 (3-12) months, respectively. Median (IQR) C5 was 7.8 (3.9-15.6) mu M/L and cough frequency 399 (181-651) coughs/24 h.Genotype frequencies were as shown (Table). There was no evidence for an association between TRPV1 polymorphisms and C5 or CF24. This was the case regardless of diagnosis.ConclusionThis small study did not provide support for a large effect of TRPV1 polymorphism on cough frequency or cough reflex sensitivity in chronic cough. However, we lacked power to detect small/modest effects.Reference Smit, et al. Respir Res 2012; 13:26.Abstract M12 Table 1TRPV1 single nucleotide polymorphism, cough reflex sensitivity and cough frequency in chronic cough TRPV1 SNPnC5 ( mu M/L)regn coeff. (95% CI) p CF24regn coeff. (95% CI) P rs161365 CC CT TT 29 18 710.4 (5.0-19.1) 6.9 (2.5-12.0) 3.9 (1.4-16.6)-0.38 (-1.07 to 0.31)0.277499 (260-840) 458 (111-636) 251 (147-362)-0.24 (-0.68 to 0.19)0.263rs17706630 GG GA AA 37 16 17.8 (4.9-15.6) 5.7 (1.3-15.6) 15.6 (n/a)-0.34 (-1.31 to 0.63)0.487436 (197-636) 362 (120-976) 154 (n/a)0.02 (-0.59 to 0.63)0.943rs2277675 TT TC CC 26 25 39.41 (5.3-15.6) 5.9 (1.9-13.8) 22.1 (3.9-49.6)0.10 (-0.68 to 0.89)0.795499 (205-635) 362 (154-1187) 104 (42-285)-0.25 (-0.74 to 0.25)0.321rs222741 AA AG GG 28 18 77.8 (3.9-15.6) 5.4 (2.5-23.0) 12.0 (7.8-16.6)0.38 (-0.31 to 1.08)0.274338 (111-636) 425 (292-738) 567 (212-611)-0.14 (-0.31 to 0.59)0.534rs150854 TT TG GG 19 28 411.0 (5.5-16.6) 6.1 (3.4-17.1) 9.8 (6.0-11.0)-0.29 (-1.18 to 0.61)0.525458 (147-611) 399 (166-1081) 448 (241-949)0.32 (-0.22 to 0.85)0.237rs224498 TT TG GG 26 22 69.8 (5.1-19.7) 7.8 (3.4-15.6) 6.7 (0.5-11.0)-0.47 (-1.19 to 0.25)0.198410 (209-636) 380 (120-634) 695 (441-1985)0.10 (-0.38 to 0.57)0.684SNP - single nucleotide polymorphism, C5 - minimum capsaicin concentration required to produce 5 coughs, CF24 - 24-hour cough frequency. Values of C5 and CF24 are median (IQR). Regression coefficients are per minor allele effects from linear regression analyses with associated p - values.