Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics

抄録

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.