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- Dahgam, Santosh, et al.
(författare)
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Haplotypes of the inducible nitric oxide synthase gene are strongly associated with exhaled nitric oxide levels in adults: a population-based study
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:7, s. 449-454
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous genetic association studies have reported evidence for association of single-nucleotide polymorphisms (SNPs) in the NOS2 gene, encoding inducible nitric oxide synthase (iNOS), to variation in levels of fractional exhaled nitric oxide (FENO) in children and adults. In this study, we evaluated 10 SNPs in the region of chromosome 17 from 26.07Mb to 26.13Mb to further understand the contribution of NOS2 to variation in levels of FENO. Methods In a cohort of 5912 adults 25-75years of age, we investigated the relationship between NOS2 haplotypes and FENO, and effect modification by asthma. Results Seven common (frequency 5%) haplotypes (H1-H7) were inferred from all possible haplotype combinations. One haplotype (H3) was significantly associated with lower levels of FENO: -5.8% (95% CI -9.8 to -1.7; p=0.006) compared with the most common baseline haplotype H1. Two haplotypes (H5 and H6) were significantly associated with higher levels of FENO: +10.7% (95% CI 5.0 to 16.7; p=0.0002) and +14.9% (95% CI 10.6 to 19.3; p=7.8x10(-13)), respectively. The effect of haplotype H3 was mainly seen in subjects with asthma (-21.6% (95% CI -33.5 to -5.9)) and was not significant in subjects without asthma (-4.2% (95% CI -8.4 to 0.2)). The p value for interaction between H3 and asthma status was 0.004. Conclusions Our findings suggest that several common haplotypes in the NOS2 gene contribute to variation in FENO in adults. We also saw some evidence of effect modification by asthma status on haplotype H3.
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| 2. |
- Dahgam, Santosh, et al.
(författare)
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Single nucleotide polymorphisms in the NOS2 and NOS3 genes are associated with exhaled nitric oxide
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:3, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- Background Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. Method In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. Results In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). Conclusion 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.
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