Abstract
Background: Air humidity is considered to be one of the main climatic triggers of asthma symptoms. Bronchospastic responses to humid air are common in asthma and may complicate the course of the disease in damp climate. Osmotic-induced reactions are likely to be mediated by hypoosmolality-sensitive ion channels TRPV4 which are widely expressed in the respiratory tract.
Objective: The aim of the study was to evaluate the effect of rs6606743 and rs7971845 SNPs of TRPV4 gene on osmotic airway hyperresponsiveness (OAH) in patients with asthma.
Methods: The study included 189 subjects diagnosed with mild or moderate uncontrolled asthma (mean age 36±0.78 years). All of them underwent spirometry before and after the bronchoprovocation challenge with 3-minute inhalation of ultrasonically nebulized distilled water (UNDW). The SNPs were genotyped by PCR-RFLP analysis.
Results: Significant association with OAH was observed for rs6606743 SNP. G was defined as a risk allele with larger prevalence in the OAH group (OR 1.58 95%CI (1.04-2.40), p=0.03). A/G+G/G genotypes in dominant model were linked with positive reaction to UNDW inhalation (p=0.03). A/G and G/G carriers had a significant decrease in FEV1 after the challenge in comparison with A/A subjects (-7.3 (-12; -3.1)% and -8.6 (-16; -4.2)% vs. -2.25 (-10.3; 2.1)%, respectively, p<0.001). rs7971845 SNP was also found to be related to OAH although to a lesser extent. Association with OAH was shown for C/C+C/G genotypes (p=0.03). FEV1 fall was minimal in G/G homozygotes and differed from C/C (p=0.01) and C/G carriers (p=0.025).
Conclusion: TRPV4 variants may serve as factors predisposing to the development of OAH in patients diagnosed with asthma.
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