The influence of TRPM8 polymorphism on the progression of bronchial obstruction in patients with chronic obstructive pulmonary disease

Abstract

Introduction. Chronic obstructive pulmonary disease (COPD) is a severe respiratory pathology, the main risk factor for which is tobacco smoking. The progression of bronchial obstruction is subject to individual variability which indicates an important role of genetic factors in the pathogenesis of COPD.Aim. To establish the possible effects of TRPM8 gene polymorphisms on the rate of bronchial obstruction progression in COPD patients.Materials and methods. The study included 134 COPD patients. All patients underwent genotyping of six TRPM8 gene polymorphisms by asymmetric LATE-PCR. In order to assess the rate of the disease progression post-bronchodilator spirometry was per­formed twice with an interval of one year and a decrease in FEV1 >50 ml was considered as the presence of progressive bronchial obstruction.Results. The patients were divided into two groups: the first group included patients with progression of bronchial obstruction (59 people), the second group included patients without progression of bronchial obstruction (75 people). When analyzing the relationship between the individual polymorphisms of TRPM8 gene and the severity of COPD progression it was found that the carriage of the C allele for rs11562975 polymorphism predominates in patients with pro­gressive obstruction. In the dominant model the frequency of GC+CC genotypes carriage among persons from the first group was 35.6% versus 10.7% in the second group (p=0.001). At the same time, the effect of polymorphism remained significant regardless of gender, age, pack-year index, baseline FEV1 and the exacerbations frequency (OR 3.7, 95% CI [1.29; 10.3], p=0.01). In addition, carriers of the C allele were characterized by a more significant annual decrease in FEV1 during the year compared with patients who had the GG genotype (-120.0 [-340.0; -30.0] ml/year vs. -20.0 [-130.0; 40.0] ml/year, respectively, p=0.002).Conclusion. The obtained results indicate that carriage of the C allele (genotypes GC and CC) for rs11562975 polymorphism of TRPM8 gene is a risk factor for a more severe course of COPD with a progressive decrease in FEV1.