title: Inducible Nitric Oxide Synthase Promoter Haplotypes and Residential Traffic-Related Air Pollution Jointly Influence Exhaled Nitric Oxide Level in Children.
abstract: BACKGROUND
  Exhaled nitric oxide (FeNO), a biomarker of airway inflammation, predicts asthma risk in children. We previously found that the promoter haplotypes in inducible nitric oxide synthase (NOS2) and exposure to residential traffic independently influence FeNO level. Because NOS2 is inducible by environmental exposures such as traffic-related exposure, we tested the hypothesis that common NOS2 promoter haplotypes modulate the relationship between residential traffic-related exposure and FeNO level in children.
  
  
  METHODS
  In a cross-sectional population-based study, subjects (N = 2,457; 7-11 year-old) were Hispanic and non-Hispanic white children who participated in the Southern California Children's Health Study and had FeNO measurements. For residential traffic, lengths of local roads within circular buffers (50m, 100m and 200m radii around homes) around the subjects' homes were estimated using geographic information system (GIS) methods. We interrogated the two most common NOS2 promoter haplotypes that were found to affect FeNO level.
  
  
  RESULTS
  The relationship between local road lengths within 100m and 200m circular buffers and FeNO level varied significantly by one of the NOS2 promoter haplotypes (P-values for interaction between road length and NOS2 promoter haplotype = 0.02 and 0.03, respectively). In children who had ≤250m of local road lengths within 100m buffer around their homes, those with two copies of the haplotype had significantly lower FeNO (adjusted geometric mean = 11.74ppb; 95% confidence intervals (CI): 9.99 to 13.80) than those with no copies (adjusted geometric mean = 15.28ppb; 95% CI: 14.04 to 16.63) with statistically significant trend of lower FeNO level with increasing number of haplotype copy (P-value for trend = 0.002). In contrast, among children who had >250m of local road lengths within 100m buffer, FeNO level did not significantly differ by the haplotype copy-number (P-value for trend = 0.34). Similar interactive effects of this haplotype and local road lengths within 200m buffer on FeNO were also observed.
  
  
  CONCLUSIONS
  Higher exposure from residential traffic nullifies the protective effect of one common NOS2 promoter haplotype on FeNO level. Regulation of traffic-related pollution may protect children's respiratory health.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.|Department of Psychiatry, Kern Medical Center, Bakersfield, California, United States of America.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Salam
authors.affiliation: Molecular Technical Operations, Siemens HealthCare Diagnostics, East Walpole, Massachusetts, United States of America.
authors.forename: Pi-Chu
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
authors.forename: Sandrah P
authors.initials: SP
authors.lastname: Eckel
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects; D045853:Exhalation / Q000187:drug effects*; D005260:Female; D006239:Haplotypes; D006798:Housing; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*
chemical_list: D000393:Air Pollutants; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II