title: Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics.
abstract: BACKGROUND
  Inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment.
  
  
  METHODS
  Asthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared.
  
  
  RESULTS
  In 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels.
  
  
  CONCLUSIONS
  The number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan. Electronic address: suguru@fmu.ac.jp.
authors.forename: Suguru
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Saito
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Atsuro
authors.initials: A
authors.lastname: Fukuhara
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Uematsu
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Misa
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Nikaido
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Fukuhara
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanino
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D045853:Exhalation; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D009569:Nitric Oxide; D007073:Immunoglobulin E; D052247:Nitric Oxide Synthase Type II
keywords: Adult asthma; Asthma; Fractional exhaled nitric oxide; Genetic polymorphism; Single nucleotide polymorphism