Effect Of Trpa1 And Trpm8 Polymorphisms On Lung Function In Copd

Background: TRPM8 and TRPA1 cation channels may serve as specific receptors of cigarette smoke, particulate matter and the other typical triggers of COPD in the respiratory tract. Previously we found TRPM8 rs11562975 may influence lung function in asthma patients and modulate effect of smoking on the formation of severe bronchial obstruction. Objectives: The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on lung function in COPD patients. Methods: The study included 114 COPD patients (mean age 59.3±0.79). Polymorphisms of TRPM8 (rs10166942, rs7577262, rs11562975, rs17868387, rs58514553, rs2052030, rs17865682) and TRPA1 (rs920829, rs7819749, rs4738202, rs959976, rs959974, rs6996723) were genotyped by LATE-PCR. Lung function was assessed by standard spirometry before and after the inhalation of 400 mcg of salbutamol. Results: Post-bronchodilator (PB) FEV1/FVC was lower in TRPM8 rs11562975 GC+CC carriers as compared to the patients with the GG genotype (43.2±1.62% vs. 48.2±1.22%, p=0.03). The GC+CC genotypes were also more frequently observed in the patients with PB FEV1<60% than in the patients with FEV≥60% (32.0% vs. 12.1%). The association was significant in multiplicative (p<0.001) and dominant genetic model after the adjustment for sex, age and pack-year index (OR 2.2 95%CI (1.13-4.19), p=0.02). Lung function was also affected by TRPA1 rs7819749 and rs959974 polymorphisms. rs7819749 TT and GG carriers differed in PB FEV1 and FEV1/FVC (39.1±2.05% vs. 49.7±1.26%, respectively, p<0.001). rs959974 GG genotype was associated with lower PB FEV1/FVC when compared to the TT genotype (42.4±2.34% vs. 49.4±1.53%, p=0.01). Conclusions:TRPM8 and TRPA1 polymorphisms influence lung function in COPD.