Effect of TRPV1 and TRPV4 genes polymorphisms on the development of airway hyperresponsiveness in patients with asthma

Abstract

Introduction. A change in the level of relative humidity of the inhaled air can lead to the appearance of symptoms of airway hyperresponsiveness (AHR) in patients with asthma. Allelic variations of the TRPV genes encoding osmotic receptors may serve as an internal factor predisposing to the development of respiratory manifestations in response to an osmotic trigger.Aim. The aim of the study was to establish the contribution of some single nucleotide polymorphisms (SNPs) of TRPV1 and TRPV4 to the development of osmotic AHR in asthma patients.Materials and methods. Three hundred patients with mild and moderate asthma were enrolled in the study. Osmotic AHR was diagnosed using bronchoprovocation tests with inhalation of distilled water, hypertonic saline (4.5% NaCl) or by treadmill exercise challenge test. Three SNPs (rs222747, rs224534 и rs8065080) of TRPV1 and two SNPs (rs6606743, rs7971845) of TRPV4 were geno- typed.Results. Carriage of the AA genotype for rs6606743 was associated with a lower probability of developing hypo-osmotic-induced bronchospasm. This result was confirmed in recessive (OR 0.43 95% CI [0.19; 0.94], p=0.02) and Logadditive (OR 0.62 95% CI [0.4; 0.96], p=0.03) inheritance models. Besides, in patients with the AA genotype, a less pronounced decrease in all basic parameters of lung function was observed as compared with GG and ΔG genotypes (ΔFVC, ΔPEF and ΔFEF75 - p<0.01; ΔFEV1 ΔFEV1/FVC, ΔFEF50 and ΔMMEF - p<0.001).Conclusion. A protective effect of the AA genotype for rs6606743 of TRPV4 was revealed in relation to the formation of hypoosmotic AHR.