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

Johanna Lepeule

Corresponding author: jlepeule@hsph.harvard.edu
Exposure, Epidemiology and Risk Program; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA

Andrea Baccarelli

Exposure, Epidemiology and Risk Program; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA

Letizia Tarantini

Center of Molecular and Genetic Epidemiology; Department of Environmental and Occupational Health; Ca’ Granda Ospedale Maggiore Policlinico IRCCS Foundation; Università degli Studi di Milano; Milan, Italy

Valeria Motta

Exposure, Epidemiology and Risk Program; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA; Center of Molecular and Genetic Epidemiology; Department of Environmental and Occupational Health; Ca’ Granda Ospedale Maggiore Policlinico IRCCS Foundation; Università degli Studi di Milano; Milan, Italy

Laura Cantone

Center of Molecular and Genetic Epidemiology; Department of Environmental and Occupational Health; Ca’ Granda Ospedale Maggiore Policlinico IRCCS Foundation; Università degli Studi di Milano; Milan, Italy

Augusto A. Litonjua

Channing Laboratory; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA; Division of Pulmonary and Critical Care Medicine; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA

David Sparrow

VA Normative Aging Study; Veterans Affairs Boston Healthcare System and the Department of Medicine; Boston University School of Medicine; Boston, MA USA

Pantel S. Vokonas

VA Normative Aging Study; Veterans Affairs Boston Healthcare System and the Department of Medicine; Boston University School of Medicine; Boston, MA USA

Joel Schwartz

Exposure, Epidemiology and Risk Program; Department of Environmental Health; Harvard School of Public Health; Boston, MA USA; Channing Laboratory; Brigham and Women’s Hospital; Harvard Medical School; Boston, MA USA

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 (FEV₁), 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 FEV₁ 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.

Received: October 12, 2011; Accepted: December 29, 2011

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