Influence of TRPV4 gene polymorphisms on the development of osmotic airway hyperresponsiveness in patients with bronchial asthma

Abstract

The effect of single nucleotide polymorphisms (SNP) of TRPV4 gene on the development of airway hyperresponsiveness (39.7% of cases) in response to the decrease in osmolarity under inspiration of distilled water aerosol was studies in 189 patients with uncontrolled bronchial asthma. rs6606743 SNP was found to significantly contribute to the development of osmotic airway hyperresponsiveness. Analysis of the dominant genetic model revealed substantial prevalence of AG + GG genotype frequency in the group of patients with asthma with osmotic hyperresponsiveness in comparison with the patients who had negative response to bronchoprovocation. In addition, carriers of GG or AG genotypes had significantly more profound decrease of lung function parameters in relation to A homozygous patients.

Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae–induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation

“…TRPV4 has also been implicated in ventilator‐induced lung injury (17) and has been shown to regulate inflammation and pulmonary function in chemically induced lung injury (18). Furthermore, TRPV4 gene polymorphisms have been shown to influence the development of osmotic airway hyper‐responsiveness in patients with bronchial asthma (19). Recently, TRPV4 has been shown to integrate soluble and mechanical signals in the differentiation of cardiac (20) and lung (21) fibroblasts; however, neither the mechanism by which TRPV4 modulates fibroblast differentiation, nor its role in airway remodeling in vivo [using TRPV4‐knockout (KO) mice] and the underlying molecular mechanism involved has been investigated.…”

Transient Receptor Potential Vanilloid channel regulates fibroblast differentiation and airway remodeling by modulating redox signals through NADPH Oxidase 4

“…Although TRPV4 is activated by physical and chemical stimuli (temperature, hypo tonicity, phorbol esters, endocannabinoids, arachidonic acid (AA) and its metabolites, epoxy eicosatrienoic acids (EETs) [40][41][42][43] , we and others recently demonstrated that TRPV4 is also activated by TGFβ 18,19,23 and play a vital role in lung remodeling. Intriguingly, TRPV4 gene polymorphisms have been shown to influence the development of osmotic airway hyperresponsiveness in patients with bronchial asthma 16 . However, the mechanism through which TRPV4 is activated or whether and how TRPV4 facilitates fibroblast differentiation and matrix remodeling, specifically in asthma, is still elusive.…”

Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation

“…Genetic variation at the TRPV4 locus has been associated with lung pathology in prior studies in humans. In particular, the G allele or AG+GG genotypes at rs6606743 were associated with osmotic airway hyperresponsiveness (Naumov et al, 2016) and increased risk of chronic obstructive pulmonary disease (Zhu et al, 2009). We therefore tested for the association of genotype at rs6606743 with fungal sensitization and asthma in 211 participants in the Childhood Origins of Asthma (COAST) study.…”