Affiliations: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA | Department of Epidemiology, University of Washington, Seattle, WA, USA | Center for Environmental Health and Technology, Department of Epidemiology and Laboratory Medicine and Pathology, Brown University, Providence, RI, USA | Masonic Cancer Center, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA | Department of Neurology, University of Washington, Seattle, WA, USA
Note: [] Correspondence to: Susan Searles Nielsen, Department of Environmental and Occupational Health Sciences, University of Washington, Box 357234, Seattle, WA 98195, USA. Tel.: +1 206 685 2487; Fax: +1 206 685 3990; E-mail: ssn@u.washington.edu
Abstract: 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). Conclusion: PD cases may have innate differences in their ability to respond to tobacco smoke.
Keywords: DNA methylation, idiopathic Parkinson's disease, long interspersed nucleotide elements, smoking
