LINE-1 基因甲基化、吸烟与帕金森病风险。
LINE-1 DNA methylation, smoking and risk of Parkinson's disease.
机构信息
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
出版信息
J Parkinsons Dis. 2012;2(4):303-8. doi: 10.3233/JPD-012129.
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.
背景
长散布核元件-1（LINE-1）逆转录转座子遍布人类基因组。那些保留完整 5'启动子的可以复制并插入表达酪氨酸羟化酶的神经祖细胞的 DNA 中，这可能会影响这些细胞的分化和存活。LINE-1 启动子甲基化与 LINE-1 传播减少有关。
目的
研究 LINE-1 启动子甲基化是否与帕金森病（PD）有关。
方法
我们比较了 292 例新诊断的 PD 病例和 401 例无神经相关的正常对照者血液单核细胞中的 LINE-1 甲基化谱，所有患者均为华盛顿州西部的非西班牙裔白种人。
结果
总体而言，PD 与 LINE-1 启动子的甲基化百分比无关。然而，PD 与从不吸烟的人群之间可预测的反比关系在 LINE-1 启动子甲基化最低的男性和女性中最强，而随着 LINE-1 甲基化的增加，这种关系变得不那么明显。在这种可能的相互作用下，经常有规律地吸烟与对照组的 LINE-1 甲基化减少有关（年龄和性别调整的线性回归β=-0.24，95%置信区间[-0.43，-0.04]），但与病例无关（β=0.06，95%置信区间[-0.17，0.28]，交互作用 p=0.06）。
结论
PD 病例可能在对烟草烟雾的反应能力上存在内在差异。
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