Genetic variation of the alpha subunit of the epithelial Na+ channel influences exhaled Na+ in healthy humans

• Published in: Respiratory physiology & neurobiology Vol. 179; no. 2-3; pp. 205 - 211
• Main Authors: Foxx-Lupo, William T., Wheatley, Courtney M., Baker, Sarah E., Cassuto, Nicholas A., Delamere, Nicholas A., Snyder, Eric M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.12.2011; Elsevier
• Subjects: ADRB2; Adult; Airway surface fluid; Beta-agonist; Biological and medical sciences; Breath condensate; Epithelial Sodium Channels - genetics; Exhalation - genetics; Female; Fundamental and applied biological sciences. Psychology; Genotype; Humans; Male; Medical Education; Polymorphism, Single Nucleotide; Pulmonary Diffusing Capacity - physiology; Pulmonary/Respiratory; Real-Time Polymerase Chain Reaction; Respiratory Function Tests; SCNN1A; Sodium - analysis; Sodium - metabolism; Vertebrates: respiratory system; Young Adult; Airway surface fluid; Beta-agonist; Breath condensate; ADRB2; SCNN1A; Human; Agonist; Ionic channel; Subunit; Respiratory system; Respiratory tract; Vertebrata; Mammalia; Sodium; Genetics
• ISSN: 1569-9048; 1878-1519; 1878-1519
• DOI: 10.1016/j.resp.2011.08.008

► We explored the influence of genetics of SCNN1A on exhaled Na+ and lung diffusion. ► We found that the AA genotype had greater decrease in exhaled Na+ with albuterol. ► Both groups had a similar increase in lung conductance with albuterol. Epithelial Na+ channels (ENaC) are located in alveolar cells and are important in β2-adrenergic receptor-mediated lung fluid clearance through the removal of Na+ from the alveolar airspace. Previous work has demonstrated that genetic variation of the alpha subunit of ENaC at amino acid 663 is important in channel function: cells with the genotype resulting in alanine at amino acid 663 (A663) demonstrate attenuated function when compared to genotypes with at least one allele encoding threonine (T663, AT/TT). We sought to determine the influence of genetic variation at position 663 of ENaC on exhaled Na+ in healthy humans. Exhaled Na+ was measured in 18 AA and 13 AT/TT subjects (age=27±8 years vs. 30±10 years; ht.=174±12cm vs. 171±10cm; wt.=68±12kg vs. 73±14kg; BMI=22±3kg/m2 vs. 25±4kg/m2, mean±SD, for AA and AT/TT, respectively). Measurements were made at baseline and at 30, 60 and 90min following the administration of a nebulized β2-agonist (albuterol sulfate, 2.5mg diluted in 3ml normal saline). The AA group had a higher baseline level of exhaled Na+ and a greater response to β2-agonist stimulation (baseline=3.1±1.8mmol/l vs. 2.3±1.5mmol/l; 30min-post=2.1±0.7mmol/l vs. 2.2±0.8mmol/l; 60min-post=2.0±0.5mmol/l vs. 2.3±1.0mmol/l; 90min-post=1.8±0.8mmol/l vs. 2.6±1.5mmol/l, mean±SD, for AA and AT/TT, respectively, p<0.05). The results are consistent with the notion that genetic variation of ENaC influences β2-adrenergic receptor stimulated Na+ clearance in the lungs, as there was a significant reduction in exhaled Na+ over time in the AA group.