Association of AQP5 gene polymorphisms with osmotic airway hyperresponsiveness in asthma

Background: Airway hyperresponsiveness (AHR) to osmotic stimuli is common and clinically relevant in asthma. AQP5 is a membrane water channel that may be functionally implicated in airway inflammation and hypersecretion. Objectives: The aim was to assess the effect of AQP5 SNPs on osmotic AHR in asthma patients. Methods: The study enrolled 274 patients with mild-to-moderate asthma, mean age 36.2±0.67 years. The patients underwent bronchoprovocation with 3-min inhalation of distilled water (hypoosmotic stimulus) and hypertonic saline aerosol (hyperosmotic stimulus). Lung function was measured by spirometry before and after each challenge. AQP5 SNPs (rs3759129, rs3736309, rs296756, rs1964676) were genotyped by LATE-PCR. Results: Association with hypoosmotic AHR was found for rs3759129 and rs296756. C allele of rs3759129 was protective against hypoosmotic AHR as AC heterozygotes had less profound response to the challenge compared to AA carriers (ΔFEV1 -1.4 (-6.3; 2.33)% vs. -5.4 (-12.0; -1.0)%, p=0.001; ΔFEF25-75 -1.0 (-18.0; 14.0)% vs. -9.1 (-21.1; 1.2)%, p=0.009). G allele of rs296756 in homozygous state also had protective effect. AA and AG (but not GG) carriers showed marked reduction in airway patency (ΔFEV1 -5,5 (-12,0; -0,8)% vs. -0,2 (-4,5; 3,4)%, p=0.004; ΔFEF25-75 -9,6 (-22,0; 2,3)% vs. 2,0 (-8,9; 9,0)%, p=0.008, for AA and GG genotypes, respectively). rs3759129 also influenced hyperosmotic AHR: all patients with the AHR had AA genotype while 27% of patients without the AHR had AC genotype (p=0.006). Conclusions:AC genotype of rs3759129 and GG genotype of rs296756 exert a protective effect on hypoosmotic AHR. AC genotype of rs3759129 also protects asthma patients from hyperosmotic AHR.