Methylated Genes in Sputum Among Older Smokers With Asthma.
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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.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.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-5?) 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.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.