title: Methylated Genes in Sputum Among Older Smokers With Asthma.
abstract: 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.
authors.affiliation: Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM.
authors.forename: Akshay
authors.initials: A
authors.lastname: Sood
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM.
authors.forename: Hans
authors.initials: H
authors.lastname: Petersen
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Blanchette
authors.affiliation: University of Colorado at Denver, Denver, CO.
authors.forename: Paula
authors.initials: P
authors.lastname: Meek
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Picchi
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Belinsky
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM. Electronic address: YTesfaig@lrri.org.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000209:etiology* / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000502:physiology; D012907:Smoking / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*