Role Of Trpm8 Polymorphisms In Predisposition To Copd Development In Smokers

Background: TRPM8 cold and menthol receptors are abundantly expressed in the respiratory tract. It has been shown TRPM8 is sensitive to cigarette smoke and can mediate inflammation and hypersecretion in the airways upon activation. Objectives: The aim of the study was to investigate the role of TRPM8 gene polymorphisms in COPD predisposition among smokers. Methods: The study included 114 COPD patients (mean age 59.3±0.79) and 105 healthy subjects with smoking history (mean age 43.1±1.13). Pack-year index was 40 (28; 49) in COPD patients and 15 (6; 22) in smokers without bronchial obstruction. Lung function was measured by standard spirometry. Polymorphisms of TRPM8 (rs10166942, rs7577262, rs11562975, rs17868387, rs58514553, rs2052030, rs17865682) were genotyped by LATE-PCR with melting analysis of molecular beacon probes. Results: Among the studied polymorphisms rs2052030 located in 3’-UTR significantly influenced COPD predisposition. The CC and GG genotypes of TRPM8 rs2052030 were more frequent in COPD patients comparing to the healthy smokers while the CG genotype was protective against COPD. CG genotype frequency was 28.6% and 52.5% in COPD and in control group, respectively. Association was significant in general (p=0.001) and over-dominant genetic model (CG vs. CC+GG, p<0.001) but not for alleles (p=0.1). In over-dominant model significance retained after correction for sex, age and pack-year index (OR 0.59 95%CI (0.41-0.86), p=0.007). Conclusions:TRPM8 rs2052030 polymorphism may influence COPD predisposition exerting protective effect in smokers in case of heterozygous CG genotype.