Gene promoter methylation is associated with lung function in the elderly: The normative aging study

Johanna Lepeule, Andrea Baccarelli, Letizia Tarantini, Valeria Motta, Laura Cantone, Augusto A. Litonjua, David Sparrow, Pantel S. Vokonas, Joel Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston. Participants donated a blood sample for DNA methylation analysis and underwent spirometry at each visit every 3 to 5 y from 1999-2006. We used separate multivariate mixed effects regression models to study the association between each lung function measurement and DNA methylation within each gene. Decreased CRAT, F3 and TLR2 methylation was significantly associated with lower lung function. One interquartile range (IQR) decrease in DNA methylation was associated with lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1), respectively by 2.94% (p <10 -4) and 2.47% (p <10 -3) for F3 and by 2.10% (p <10 -2) and 2.42% (p <10 -3) for TLR2. Decreased IFNγ and IL6 methylation was significantly associated with better lung function. One IQR decrease in DNA methylation was associated with higher FEV 1 by 1.75% (p = 0.02) and 1.67% (p = 0.05) for IFNγ and IL6, respectively. These data demonstrate that DNA methylation may be part of the biological processes underlying the lung function decline and that IFNγ and IL6 may have ambivalent roles through activation of negative feedback.

Original languageEnglish
Pages (from-to)261-269
Number of pages9
JournalEpigenetics
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • DNA methylation
  • F3
  • FEV
  • GCR
  • Genes
  • INOS
  • Lungs
  • OGG1
  • Spirometry
  • TLR2

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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