US EPA

2267440 

Journal Article 

Abstract 

Genetic determinants of exhaled nitric oxide concentrations in children using a genome-wide association study 

Salam, MT; Islam, T; Gauderman, WJ; Gilliland, FD 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A4006 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A4006 

WOS:000208771003351 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

Rationale: Exhaled nitric oxide (FeNO) is a biomarker of airway inflammation and oxidative/nitrosative stress in the airways. Because genetic determinants of FeNO remain largely unknown, we were interested in identifying variations in genome that were associated with FeNO concentration in children using a genome-wide association study and whether race/ethnicity, and history of asthma and respiratory allergy influenced these genetic associations.

Methods: Among 1,515 non-Hispanic and Hispanic white children (mean age 8.4 years) of the southern California Children's Health Study, both genome-wide genotype and FeNO data were available. Online FeNO (50ml/sec) was estimated from offline measurement (at 100ml/sec flow) using a validated prediction model and was log transformed. Illumina HumanHap550 or Human 610-Quad BeadChip platforms were used for genotyping. FeNO measured in 1,714 children in another year was used to validate the findings of the discovery population. Of them, 309 children that did not have FeNO measurement in previous year served as replication sample. Linear regression models were fitted to compute estimates of the association between the genetic variants and FeNO level adjusting for age, community of residence, race/ethnicity, ancestry (African, European, American Indian, and East Asian), and history of asthma and respiratory allergy.

Results: In the discovery sample, two single nucleotide polymorphisms (SNPs) were associated with FeNO but the p-value did not reach genome-wide significance (P < 2.38 x 10^-7). The SNPs rs2297185 and rs1413178 were associated with lower and higher FeNO, respectively. These associations were similar in the validation sample (both P ≤ 0.04) and in the replication sample (not statistically significant). Race/ethnicity, asthma or respiratory allergy status did not influence the associations between these SNPs and FeNO level (all P-values for interaction > 0.05)

Conclusion: These results highlight the need for a larger collaborative study in identifying the genetic determinants of FeNO level. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010