Alu and LINE-1 methylation and lung function in the normative ageing study.
OBJECTIVE
To investigate the association between methylation of transposable elements Alu and long-interspersed nuclear elements (LINE-1) and lung function.


METHODS
Cohort study.


METHODS
Outpatient Veterans Administration facilities in greater Boston, Massachusetts, USA.


METHODS
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.


METHODS
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 (FEV(1)) (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 FEV(1)/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 FEV(1) (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.
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nancy E
NE
Lange
Joanne
J
Sordillo
Letizia
L
Tarantini
Valentina
V
Bollati
David
D
Sparrow
Pantel
P
Vokonas
Antonella
A
Zanobetti
Joel
J
Schwartz
Andrea
A
Baccarelli
Augusto A
AA
Litonjua
Dawn L
DL
Demeo