title: Polymorphic Variants 279R and 668Q Augment Activity of Matrix Metalloproteinase-9 in Breath Condensates of Children with Asthma.
abstract: Matrix metalloproteinase (MMP)-9 is involved in pathophysiology of asthma, mainly asthma-associated airway remodeling. Exhaled breath condensates (EBC) of asthmatics contain increased amounts of MMP-9 with activity higher, than in healthy controls. The increased activity of MMP-9 may originate from its excessive production and activation, but may also result from variations in MMP-9 structure, which are determined by single nucleotide polymorphisms (SNPs). In this pilot study we aimed to assess the possible influence of two functional MMP-9 polymorphisms, Q279R and R668Q, on enzymatic activity of MMP-9, measured in EBC of asthmatic children. The concentration and activity of MMP-9 were analyzed in EBC of 20 children with allergic asthma using specific standard ELISA and novel immunoenzymatic activity assay. The SNPs of MMP-9 were assessed using real-time PCR-based genotyping test. We have found that MMP-9 concentration in breath condensates of children with stable asthma was slightly higher in ELISA, than in the activity assay. Moreover, these results and activity-to-amount ratio have revealed some relationship with a presence of specific 279R and/or 668Q MMP-9 gene variants. Our observation suggests that at least in some patients MMP-9 hyperactivity may result from genetic predisposition, determined by polymorphic variants of MMP-9 gene. Moreover, it supports previous reports postulating significance of MMP-9 in pathogenesis of asthma. However, this issue still requires further studies.
authors.affiliation: Department of Paediatrics, Pneumonology and Allergology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grzela
authors.affiliation: Department of Paediatrics, Pneumonology and Allergology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Zagórska
authors.affiliation: Department of Histology and Embryology, Medical University of Warsaw, Chalubinskiego 5, 02-004, Warsaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Krejner
authors.affiliation: Department of Histology and Embryology, Medical University of Warsaw, Chalubinskiego 5, 02-004, Warsaw, Poland.|Potgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.|Department of Otolaryngology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Litwiniuk
authors.affiliation: Department of Paediatrics, Pneumonology and Allergology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Zawadzka-Krajewska
authors.affiliation: Department of Paediatrics, Pneumonology and Allergology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kulus
authors.affiliation: Department of Histology and Embryology, Medical University of Warsaw, Chalubinskiego 5, 02-004, Warsaw, Poland. tomekgrzela@gmail.com.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grzela
mesh_terms: D000293:Adolescent; D056151:Airway Remodeling; D001249:Asthma / Q000378:metabolism*; D001944:Breath Tests; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D045853:Exhalation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide
chemical_list: C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: ASTHMA; Airway remodeling; Enzyme activity; Exhaled breath condensate; Matrix metalloproteinase; Single nucleotide polymorphism