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2616787 
Journal Article 
Abstract 
Particulate air pollution modifies methylation of NFKb pathways 
Schwartz, J; Sofer, T; Maity, A; Lin, X; Baccarelli, A 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A4008 
English 
WOS:000208771003353 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Background:Air pollution is associated with heart and lung disease, and one mechanism identified in toxicology and epidemiology studies involves increased inflammation. Some toxicology studies indicate that NFKb pathways are involved but there is no human low dose confirmation of this. Methylation of the promoter regions of genes can modify gene expression.

Methods: We examined CpG methylation of promoter regions of genes on the NFKb pathway (identified in Biocarta) in 141 elderly subjects in the Normative Aging Study using a Nimblegen array. To address effects along the entire pathway while controlling for multiple comparisons we undertook a staged, sparse canonical correlation analysis (CCA). We divided the sample in two, and in the first 70 subjects we identified a subset of genes whose correlation with exposure was highest, using an analogue to Akaike’s information Criterion to penalize higher degree of freedom models. We then used the chosen model to create a methylation score for the remaining 71 subjects and calculated the correlation (and significance) of this score with air pollution. We found significant associations of both black carbon, a marker for traffic particles and PM2.5 with methylation along the NFKb pathway. The correlation between methylation score and BC was 0.34 (p=0.029) and the CCA chose 8 genes as contributing to the association. For PM2.5 the correlation was 0.33 (p=0.009) and 7 genes contributed to the association.

Conclusions: Methylation changes along the NFKb pathway may be an important component of particle toxicity. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010 
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