Alu and LINE-1 methylation and lung function in the normative ageing study

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Alu and LINE-1 methylation and lung function in the normative ageing study

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Title: Alu and LINE-1 methylation and lung function in the normative ageing study
Author: Lange, Nancy E; Sordillo, Joanne; Tarantini, Letizia; Bollati, Valentina; Sparrow, David; Vokonas, Pantel; Zanobetti, Antonella; Schwartz, Joel David; Baccarelli, Andrea; Litonjua, Augusto Ampil; Demeo, Dawn Lisa

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Citation: Lange, Nancy E, Joanne Sordillo, Letizia Tarantini, Valentina Bollati, David Sparrow, Pantel Vokonas, Antonella Zanobetti, et al. 2012. Alu and LINE-1 methylation and lung function in the normative ageing study. BMJ Open 2(5): e001231.
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Abstract: Objectives: To investigate the association between methylation of transposable elements Alu and long-interspersed nuclear elements (LINE-1) and lung function. Design: Cohort study. Setting: Outpatient Veterans Administration facilities in greater Boston, Massachusetts, USA. Participants: Individuals from the Veterans Administration Normative Aging Study, a longitudinal study of aging in men, evaluated between 1999 and 2007. The majority (97%) were white. Primary and secondary outcome measures: Primary predictor was methylation, assessed using PCR-pyrosequencing after bisulphite treatment. Primary outcome was lung function as assessed by spirometry, performed according to American Thoracic Society/European Respiratory Society guidelines at the same visit as the blood draws. Results: In multivariable models adjusted for age, height, body mass index (BMI), pack-years of smoking, current smoking and race, Alu hypomethylation was associated with lower forced expiratory volume in 1 s (FEV1) (β=28 ml per 1% change in Alu methylation, p=0.017) and showed a trend towards association with a lower forced vital capacity (FVC) (β=27 ml, p=0.06) and lower FEV1/FVC (β=0.3%, p=0.058). In multivariable models adjusted for age, height, BMI, pack-years of smoking, current smoking, per cent lymphocytes, race and baseline lung function, LINE-1 hypomethylation was associated with more rapid decline of FEV1 (β=6.9 ml/year per 1% change in LINE-1 methylation, p=0.005) and of FVC (β=9.6 ml/year, p=0.002). Conclusions: In multiple regression analysis, Alu hypomethylation was associated with lower lung function, and LINE-1 hypomethylation was associated with more rapid lung function decline in a cohort of older and primarily white men from North America. Future studies should aim to replicate these findings and determine if Alu or LINE-1 hypomethylation may be due to specific and modifiable environmental exposures.
Published Version: doi:10.1136/bmjopen-2012-001231
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488751/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10581400
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