NFE2L2、PPARGC1α 与农药和帕金森病风险及进展。
NFE2L2, PPARGC1α, and pesticides and Parkinson's disease risk and progression.
机构信息
Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA; Departments of Human Genetics and Biomathematics, David Geffen School of Medicine, Los Angeles, CA, USA.
出版信息
Mech Ageing Dev. 2018 Jul;173:1-8. doi: 10.1016/j.mad.2018.04.004. Epub 2018 Apr 6.
OBJECTIVE
To investigate three expression-altering NFE2L2 SNPs and four PPARGC1α previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression.
METHODS
In 472 PD patients and 532 population-based controls, we examined variants and their interactions with maneb and paraquat (MB/PQ) pesticide exposure on PD onset (logistic regression) and progression of motor symptoms and cognitive decline (n = 192; linear repeated measures).
RESULTS
NFE2L2 rs6721961 T allele was associated with a reduced risk of PD (OR = 0.70, 95% CI = 0.53, 0.94) and slower cognitive decline (β = 0.095; p = 0.0004). None of the PPARGC1α SNPs were marginally associated with PD risk. We estimate statistical interactions between MB/PQ and PPARGC1α rs6821591 (interaction p = 0.009) and rs8192678 (interaction p = 0.05), such that those with high exposure and the variant allele were at an increased risk of PD (OR ≥ 1.30, p ≤ 0.05). PPARGC1α rs6821591 was also associated with faster motor symptom progression as measured with the UPDRS-III (β = 0.234; p = 0.001).
CONCLUSION
Our study provides support for the involvement of both NFE2L2 and PPARGC1α in PD susceptibility and progression, marginally and through pathways involving MB/PQ exposure.
目的
研究先前与帕金森病（PD）风险和症状进展相关的三个改变 NFE2L2 表达的 SNP 和四个改变 PPARGC1α 表达的 SNP 以及农药。
方法
在 472 名 PD 患者和 532 名基于人群的对照中，我们研究了变异及其与代森锰锌和百草枯（MB/PQ）农药暴露对 PD 发病（逻辑回归）和运动症状及认知下降进展的相互作用（n=192；线性重复测量）。
结果
NFE2L2 rs6721961 T 等位基因与 PD 风险降低相关（OR=0.70，95%CI=0.53，0.94）和认知下降速度较慢（β=0.095；p=0.0004）。PPARGC1α 中没有一个 SNP 与 PD 风险有边缘相关性。我们估计了 MB/PQ 与 PPARGC1α rs6821591（交互作用 p=0.009）和 rs8192678（交互作用 p=0.05）之间的统计学相互作用，使得那些高暴露和变异等位基因的人患 PD 的风险增加（OR≥1.30，p≤0.05）。PPARGC1α rs6821591 也与 UPDRS-III 测量的运动症状进展更快相关（β=0.234；p=0.001）。
结论
我们的研究为 NFE2L2 和 PPARGC1α 均参与 PD 易感性和进展提供了支持，这些作用具有边缘相关性，并通过涉及 MB/PQ 暴露的途径发挥作用。
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