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.
Mech Ageing Dev. 2018 Jul;173:1-8. doi: 10.1016/j.mad.2018.04.004. Epub 2018 Apr 6.
To investigate three expression-altering NFE2L2 SNPs and four PPARGC1α previously implicated SNPs and pesticides on Parkinson's disease (PD) risk and symptom progression.
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).
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).
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.
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。
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）。
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）。
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。
