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Original Research |

Methylated Genes in Sputum Among Older Smokers With AsthmaMethylated Genes in Sputum and Asthma

Akshay Sood, MD, MPH, FCCP; Hans Petersen, MS; Christopher M. Blanchette, PhD; Paula Meek, PhD, RN; Maria A. Picchi, MPH; Steven A. Belinsky, PhD; Yohannes Tesfaigzi, PhD
Author and Funding Information

From the Department of Medicine (Dr Sood), University of New Mexico School of Medicine; and the Lovelace Respiratory Research Institute (Mr Petersen; Drs Blanchette, Belinsky, and Tesfaigzi; and Ms Picchi), Albuquerque, NM; and the University of Colorado at Denver (Dr Meek), Denver, CO.

Correspondence to: Yohannes Tesfaigzi, PhD, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108; e-mail: YTesfaig@lrri.org


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This study was supported by the State of New Mexico (appropriation from the Tobacco Settlement Fund) and from the National Institutes of Health [Grants K23 HL 094531-01 and CTSA 1ULRR031977-01 (A. S.), RO1 ES015482 (Y. T.), and R01 CA 097356 (S. B.)].


Chest. 2012;142(2):425-431. doi:10.1378/chest.11-2519
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Objective:  The epigenetic basis for human asthma is not well studied, particularly among older adults. This study investigated the methylation profiles in sputum DNA among older adults with asthma, using a population of smokers.

Methods:  This was a cross-sectional study using the Lovelace Smokers Cohort, a population of former and current smokers aged ≥ 40 years in New Mexico. One hundred eighty-four smokers with asthma were compared with 511 smoker control subjects with a similar smoking history, after carefully excluding those with COPD. Environmental exposures were assessed by a standard questionnaire. Postbronchodilator spirometry was performed. Induced sputum was analyzed for the methylation prevalence of 12 selected asthma-related genes using nested methylation-specific polymerase chain reaction assay.

Results:  Asthma was associated with a greater number of methylated genes and, specifically, with methylated protocadherin-20 gene in sputum DNA compared with control subjects with a similar smoking history. These associations remained significant after adjustment for covariates as well as Bonferroni correction. A synergistic interaction was noted between two methylated genes (protocadherin-20 and paired box protein transcription factor-5α) in sputum DNA on the odds for asthma (P = .009). Interestingly, the epigenetic-asthma associations were not explained by the environmental factors studied. Further, methylated genes in sputum DNA, including the protocadherin-20 gene, identified a symptomatically more severe asthma phenotype in a subgroup analysis.

Conclusions:  Asthma is associated with methylation of selected genes, such as protocadherin-20 gene, in sputum DNA. If future studies establish causality, novel demethylating interventions to prevent and treat asthma among older smokers may be possible.

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