title: Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.
abstract: S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.
authors.affiliation: Dept of Paediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Nadzeya V
authors.initials: NV
authors.lastname: Marozkina
authors.affiliation: Dept of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Dept of Chemistry, University of Virginia, Charlottesville, VA, USA.
authors.forename: Vitali
authors.initials: V
authors.lastname: Stsiapura
authors.affiliation: Dept of Paediatrics, Emory University, Atlanta, GA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Fitzpatrick
authors.affiliation: Dept of Paediatrics, University of Padua, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carraro
authors.affiliation: Dept of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.affiliation: Dept of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bleecker
authors.affiliation: Dept of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Meyers
authors.affiliation: Dept of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: Nizar
authors.initials: N
authors.lastname: Jarjour
authors.affiliation: Dept of Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Fain
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Wenzel
authors.affiliation: Dept of Medicine, University of Wisconsin, Madison, WI, USA.
authors.forename: William
authors.initials: W
authors.lastname: Busse
authors.affiliation: Dept of Medicine, Washington University, St. Louis, MO, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.affiliation: Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Reynold A
authors.initials: RA
authors.lastname: Panettieri
authors.affiliation: Dept of Medicine, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Moore
authors.affiliation: Dept of Paediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: Dept of Paediatrics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Palmer
authors.affiliation: Dept of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
authors.forename: Talissa
authors.initials: T
authors.lastname: Altes
authors.affiliation: Dept of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
authors.forename: Eduard E
authors.initials: EE
authors.lastname: de Lange
authors.affiliation: Dept of Pathobiology, Cleveland Clinic, Cleveland, OH, USA Dept of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Serpil
authors.initials: S
authors.lastname: Erzurum
authors.affiliation: Dept of Paediatrics, University of Virginia, Charlottesville, VA, USA.
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.affiliation: Dept of Paediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, OH, USA benjamin.gaston@case.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
mesh_terms: D000293:Adolescent; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D001249:Asthma / Q000201:enzymology*; D001706:Biopsy; D001980:Bronchi / Q000201:enzymology*; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D008297:Male; D008660:Metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000201:enzymology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D018793:Interleukin-13; D007073:Immunoglobulin E; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent