Genetic variation in inducible nitric oxide synthase promoter, residential traffic related air pollution and exhaled nitric oxide in children

2013-07-29Background: Fractional concentration of nitric oxide in exhaled air (FeNO) is a biomarker of airway inflammation. Nitric oxide synthase 2 (NOS2) in airway epithelium has been recognized as the major source of NO in exhaled breath. Earlier work has shown that common promoter haplotypes in NOS2 and total length of local roads around homes, a metric of residential traffic related pollution, affect FeNO level in children. ❧ Aims: The aims of this study were to examine the joint associations of NOS2 promoter haplotypes and length of local roads around homes and FeNO and to assess the influence of asthma on these associations in children. ❧ Methods: The study included 2,457 (7 to 11 year-old) children of the Southern California Children’s Health Study. FeNO was measured at school during 2005-2006. Lengths of local roads within circular buffers (50m, 100m and 200m) around the participant residence were estimated using GIS methods. Two common promoter haplotypes in NOS2 that have been associated with FeNO, asthma and lung function growth in children were selected. Linear regression was utilized to examine the independent and joint associations of NOS2 promoter haplotypes and road length measures on FeNO. ❧ Results: We observed joint effects of length of local roads within 100m and 200m buffer and the most common haplotype for FeNO (P-values for interaction ≤0.03). In children who had ≤250m of road within 100m buffer around home, those with two copies of the haplotype had significantly lower FeNO (adjusted mean FeNO=10.71ppb; 95% confidence intervals (CI): 9.10-12.61) than those with no copies (adjusted mean FeNO 14.18ppb; 95% CI: 13.09-15.36). This protective effect of the haplotype was not observed in children who had >250m road lengths within 100m buffer. Similar joint effects of this haplotype and road lengths within 200m buffer on FeNO was observed. These joint effects were not influenced by asthma. ❧ Conclusion: Our results indicate that the protective effect of a common NOS2 promoter haplotype on NO synthesis in the airway is not evident in children who live near higher levels of local traffic