Effect of TRPM8 and TRPA1 Polymorphisms on COPD Predisposition and Lung Function in COPD Patients.

Denis E Naumov,Ivana Y Sugaylo,Elizaveta G Sheludko,Evgeniya Y Afanas'Eva,Dina A Gassan,Juliy M Perelman,Olesya O Kotova

doi:10.3390/jpm11020108

Abstract

Certain transient receptor potential (TRP) channels including TRPM8 and TRPA1 are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter—the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%. Lung function was measured by spirometry. TRPM8 and TRPA1 polymorphisms were genotyped by LATE-PCR. None of the polymorphisms significantly influenced COPD predisposition after correction for covariates and multiple testing. Among COPD patients, the TT genotype of TRPA1 rs7819749 was significantly associated with higher degree of bronchial obstruction. In addition, we established that carriers of the C allele of TRPM8 rs11562975 more commonly had post-bronchodilator FEV1 < 60% (OR 3.2, 95%CI (1.14–8.94), p = 0.03) and revealed the effect of TRPA1 rs959976 and TRPM8 rs17865682 on bronchodilator response in COPD. Thus, the obtained results suggest possible involvement of TRPM8 and TRPA1 in COPD pathogenesis, indicating the necessity to further investigate their functional role in this pathology.

Highlights

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases [1]
We replicated the effect of TRPM8 rs11562975 on lung function that was previously found in smoking asthma patients [33]
In the present study we discovered the variants of TRPM8 and TRPA1 genes that may probably influence COPD predisposition and lung function in European population which suggests the potential importance of these cationic channels in COPD pathogenesis

Summary

Introduction

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases [1]. An increase of 68.9% in COPD cases has been observed over a twenty-year period worldwide, mainly at the expense of urban populations [2]. Since 2010, COPD has become the third leading cause of death, with mortality rate up to 141 per 100,000 person-years, in some countries [3]. The presence of different clinical phenotypes of COPD with corresponding underlying pathogenesis implies the urge for a personalized approach in disease management and the discovery of novel pharmacological targets [4]

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