Abstract
Osmolarity of the airways being influenced by air humidity serves as an important factor affecting lung function. It has been shown that high as well as low humidity may provoke bronchoconstriction in patients with asthma. TRPV1, TRPV2 and TRPV4 cation channels are expressed in the respiratory tract and were shown to mediate responses to hyper- and hypoosmotic stimuli.
The aim of the study was to investigate the effect of Thr469Ile and Ile585Val SNPs of TRPV1 gene and c.-323A>G SNP of TRPV2 gene on hypo- and hyperosmotic airway hyperresponsiveness (AH) in asthma.
Methods: The study involved 116 patients diagnosed with mild or moderate persistent uncontrolled asthma. All subjects underwent spirometry before and after the challenge tests with inhalation of nebulized distilled water (DW), hypertonic saline (HS) and test with physical exercise (PE). FEV1 fall by 10% or more was considered as a positive response. SNPs were genotyped by PCR with RFLP analysis.
Results: AA genotype and A allele of c.-323A>G SNP were significantly associated with hypoosmotic AH. Carriers of AA genotype prevailed among the patients with the AH (69% vs 48.6%, p=0.02 for additive model). Frequency of A allele was also higher in these patients (84.5% vs 68.6%, p=0.02; OR 2.5 95%CI (1.13-5.53)). Thr469Ile SNP was found to influence AH to PE. Ile469Ile variant comprised 31% of patients with positive response and only 7% in the group without the AH (p=0.04). No SNPs were associated with hyperosmotic AH to HS.
Conclusion: TRPV1 and TRPV2 SNPs may serve as factors predisposing to the development of AH to DW and PE in patients with asthma.
The study was supported by RSF (14-25-00019).
- Copyright ©the authors 2016
