LINE-1 DNA methylation, smoking and risk of Parkinson's disease.
BACKGROUND
Long interspersed nucleotide element-1 (LINE-1) retrotransposons are located throughout the human genome. Those retaining an intact 5' promoter can copy and insert themselves into the DNA of neural progenitor cells that express tyrosine hydroxylase, which may influence differentiation and survival of these cells. LINE-1 promoter methylation is associated with decreased LINE-1 propagation.


OBJECTIVE
To investigate whether LINE-1 promoter methylation is associated with Parkinson's disease (PD).


METHODS
We compared LINE-1 methylation profiles in blood mononuclear cells between 292 newly diagnosed PD cases and 401 unrelated, neurologically normal controls, all non-Hispanic Caucasians in western Washington state.


RESULTS
Overall, PD was not associated with percent methylation of the LINE-1 promoter. However, the predictable inverse association between PD and ever smoking tobacco was strongest for men and women with the lowest LINE-1 promoter methylation, and less apparent as LINE-1 methylation increased. Underlying this possible interaction, ever regularly smoking tobacco was associated with decreased LINE-1 methylation in controls (age- and sex-adjusted linear regression β = -0.24, 95% confidence interval [CI] -0.43, -0.04), but not in cases (β = 0.06, 95% CI -0.17, 0.28, interaction p = 0.06).


CONCLUSIONS
PD cases may have innate differences in their ability to respond to tobacco smoke.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA. ssn@u.washington.edu
Susan
S
Searles Nielsen
Harvey
H
Checkoway
Rondi A
RA
Butler
Heather H
HH
Nelson
Federico M
FM
Farin
W T
WT
Longstreth
Gary M
GM
Franklin
Phillip D
PD
Swanson
Karl T
KT
Kelsey
D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics