title: Genetic variation of the alpha subunit of the epithelial Na+ channel influences exhaled Na+ in healthy humans.
abstract: Epithelial Na(+) channels (ENaC) are located in alveolar cells and are important in β(2)-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±12 cm vs. 171±10 cm; wt.=68±12 kg vs. 73±14 kg; BMI=22±3 kg/m(2) vs. 25±4 kg/m(2), mean±SD, for AA and AT/TT, respectively). Measurements were made at baseline and at 30, 60 and 90 min following the administration of a nebulized β(2)-agonist (albuterol sulfate, 2.5 mg diluted in 3 ml normal saline). The AA group had a higher baseline level of exhaled Na(+) and a greater response to β(2)-agonist stimulation (baseline=3.1±1.8 mmol/l vs. 2.3±1.5 mmol/l; 30 min-post=2.1±0.7 mmol/l vs. 2.2±0.8 mmol/l; 60 min-post=2.0±0.5 mmol/l vs. 2.3±1.0 mmol/l; 90 min-post=1.8±0.8 mmol/l vs. 2.6±1.5 mmol/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 β(2)-adrenergic receptor stimulated Na(+) clearance in the lungs, as there was a significant reduction in exhaled Na(+) over time in the AA group.
authors: Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ 85721, United States.
authors: William T
authors: WT
authors: Foxx-Lupo
authors: Courtney M
authors: CM
authors: Wheatley
authors: Sarah E
authors: SE
authors: Baker
authors: Nicholas A
authors: NA
authors: Cassuto
authors: Nicholas A
authors: NA
authors: Delamere
authors: Eric M
authors: EM
authors: Snyder
mesh_terms: D000328:Adult; D053503:Epithelial Sodium Channels / Q000235:genetics*; D045853:Exhalation / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012129:Respiratory Function Tests; D012964:Sodium / Q000032:analysis* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D053503:Epithelial Sodium Channels; C507045:SCNN1A protein, human; D012964:Sodium