Single nucleotide polymorphisms in theNOS2andNOS3genes are associated with exhaled nitric oxide

Abstract

These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.

Occupational asthma phenotypes identified by increased fractional exhaled nitric oxide after exposure to causal agents

“…Other potential confounding factors, such as genetic polymorphism, could not be assessed in this study but may have clinical implications. 26 Sputum eosinophil counts have been shown to increase in the majority of subjects with OA after exposure to the offending agent. Although there was a correlation between the change in sputum eosinophil counts and the FENO levels before and after exposure to the offending agent, the correlation was weak in our population.…”

Haplotypes of the inducible nitric oxide synthase gene are strongly associated with exhaled nitric oxide levels in adults: a population-based study

“…Several candidate gene association studies in both children and adults focusing on NOS genes have reported that polymorphisms in the NOS2 gene influence levels of FENO,10–12 and the importance of NOS2 for FENO was very recently confirmed by a GWAS of FENO in children that identified three variants significantly associated with FENO at a genome-wide level; one of these was a single-nucleotide polymorphism (SNP) (rs944722) in NOS2 13. In terms of the more focused candidate gene studies, we reported in a previous study two tag SNPs in NOS2 , rs9901734 and rs3729508, that were associated with FENO levels in adults without asthma or respiratory symptoms or atopy 12. A recent study by Bouzigon et al also provided evidence of a relationship between SNPs in the NOS2 gene and FENO in non-asthmatic adults 11.…”

“…So far, only our previous study and two others have attempted to study the association between polymorphisms in the NOS2 gene and FENO levels in either adults or children using a candidate gene approach 10–12. In children, various SNPs including rs2297512, rs2774894, rs8081248 and rs4796017 (Salam et al 10), and in adults rs9901734, rs2297514 (Dahgam et al 12) and, most recently, rs12601458, rs6505510 (Bouzigon et al 11) have been reported to be associated with FENO among subjects without asthma. In our analysis, of the 10 investigated SNPs selected from our study and Salam et al, 5 showed significant, and independent, evidence of association with FENO levels.…”

“…10 12 Six SNPs (rs9901734, rs2297514, rs2248814, rs12944039, rs3729508 and rs2779248) were main findings from our previous analysis 12. The remaining four SNPs (rs4796017, rs2297520, rs9895453 and rs10459953) were SNPs from the Salam et al Southern California Children's Health Study10 that either were not in close linkage disequilibrium (LD) with any of our earlier findings (their SNP rs4796017) or (their SNPs rs2297520, rs9895453 and rs10459953) were alternative markers in moderate-to-high LD with one of our main findings (rs3729508), as potential alternative better markers for this finding and to ensure successful genotyping of at least one marker for this finding across the entire population sample.…”

“…Stepwise regression in a forward approach was performed in SAS (V.9.2, SAS Institute) assuming five different genetic models as previously described12 to find a subset of SNPs in the NOS2 gene that were strongly associated with FENO. The SNPs all had prior significant evidence of association with FENO, and nominal p values were used for the purpose of ranking SNPs in the selection process.…”