title: Polymorphisms in the nitric oxide synthase 1 gene are associated with severe chronic rhinosinusitis.
abstract: BACKGROUND
  Nitric oxide (NO), is a biological messenger molecule and a component of innate immunity, with important roles in the regulation of inflammation and in defense against bacterial biofilms. Polymorphisms in genes regulating NO production have the potential for a role in the development of chronic rhinosinusitis (CRS). The purpose of this study was to determine whether polymorphisms in genes regulating NO synthesis are associated with CRS.
  
  
  METHODS
  An established population of 206 individuals with severe CRS and 196 postal code-matched controls was previously screened using a pooling genome-wide associations study to estimate allelic frequency. Genes regulating NO synthesis with a maximal probability of association were identified. High-probability single nucleotide polymorphisms SNPs from the NO synthase (NOS1) and its ligand NOS1 adaptor protein (NOS1AP) genes were retained for individual genotyping. PLINK software was used to determine association.
  
  
  RESULTS
  Sixteen SNPs were genotyped successfully with a genotype distribution in agreement with Hardy-Weinberg equilibrium. Two SNPs for NOS1 (rs1483757 and rs9658281) were significantly associated with CRS, with a protective effect. The severe subphenotype showed stronger associations. Subgroup analysis for the presence of nasal polyps, origin, and gender did not influence strength of associations.
  
  
  CONCLUSIONS
  These data suggest that polymorphisms in the NOS1 gene may play a role in the susceptibility to develop CRS. Study findings apply to patients with severe CRS, unresponsive to surgery.
authors.affiliation: Department of Otolaryngology-head and Neck Surgery, Hôtel-Dieu de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montreal, QC, Canada.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Leandra Mfuna
authors.initials: LM
authors.lastname: Endam
authors.forename: Abdelali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.forename: Roberto
authors.initials: R
authors.lastname: Castano
authors.forename: Martin
authors.initials: M
authors.lastname: Desrosiers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488081:NOS1AP protein, human; D052248:Nitric Oxide Synthase Type I