Document Detail

Genetic variation of SCNN1A influences lung diffusing capacity in cystic fibrosis.
MedLine Citation:
PMID:  22776878     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Epithelial Na channels (ENaCs) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF), Na hyperabsorption results from ENaC overactivity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC α-subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the αT663 variant resulting in a more active channel.
METHODS: We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume, and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF (10 homozygous for αA663 (AA group) and 8 with at least one T663 allele (AT/TT group)). Because of the more active channel, we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise because of exercise-mediated ENaC inhibition and subsequent attenuation of Na hyperabsorption.
RESULTS: The AT/TT group had significantly lower pulmonary function, weight, and body mass index than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO = 18 ± 11 vs 41 ± 38; DLNO/VA = 14 ± 21 vs 40 ± 37; DM = 15 ± 11 vs 41 ± 38, AA vs AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise.
CONCLUSION: These results suggest that genetic variation of the α-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF.
Sarah E Baker; Eric C Wong; Courtney M Wheatley; William T Foxx-Lupo; Marina G Martinez; Mary A Morgan; Ryan Sprissler; Wayne J Morgan; Eric M Snyder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medicine and science in sports and exercise     Volume:  44     ISSN:  1530-0315     ISO Abbreviation:  Med Sci Sports Exerc     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-05-10     Revised Date:  2014-01-15    
Medline Journal Info:
Nlm Unique ID:  8005433     Medline TA:  Med Sci Sports Exerc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2315-21     Citation Subset:  IM; S    
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MeSH Terms
Carbon Monoxide / metabolism
Cystic Fibrosis / genetics,  physiopathology*
Epithelial Sodium Channels / metabolism*
Exercise / physiology
Genetic Variation*
Nitric Oxide / metabolism
Oxygen Consumption / physiology
Pulmonary Diffusing Capacity / genetics*,  physiology
Young Adult
Grant Support
Reg. No./Substance:
0/Epithelial Sodium Channels; 0/SCNN1A protein, human; 31C4KY9ESH/Nitric Oxide; 7U1EE4V452/Carbon Monoxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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