Zhang Lijun, Wang Xue, Wang Ming, Sterling Nick W, Du Guangwei, Lewis Mechelle M, Yao Tao, Mailman Richard B, Li Runze, Huang Xuemei
Institute for Personalized Medicine, Pennsylvania State University College of Medicine-Milton S. Hershey Medical Center, Hershey, PA, United States.
Department of Industrial and Manufacturing Engineering, Pennsylvania State University, University Park, PA, United States.
Front Neurol. 2017 Sep 27;8:501. doi: 10.3389/fneur.2017.00501. eCollection 2017.
A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link.
Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1) were chosen as confounding variables because they may influence both cholesterol levels and PD risk. First, the marginal structure model was applied, where the associations of total- and LDL-cholesterol levels with genetic polymorphisms, statin usage, and smoking history were estimated using linear regression. Then, potential causal influences of total- and LDL-cholesterol on PD occurrence were investigated using a generalized propensity score approach in the second step.
Both statins ( < 0.001) and LRP1 ( < 0.03) influenced total- and LDL-cholesterol levels. There also was a trend for APOE to affect total- and LDL-cholesterol ( = 0.08 for both), and for LRPAR1 to affect LDL-cholesterol ( = 0.05). Conversely, LDLR did not influence plasma cholesterol levels ( > 0.19). Based on propensity score methods, lower total- and LDL-cholesterol were significantly linked to PD ( < 0.001 and = 0.04, respectively).
The current study suggests that circulating total- and LDL-cholesterol levels potentially may be linked to the factor(s) influencing PD risk. Further studies to validate these results would impact our understanding of the role of cholesterol as a risk factor in PD, and its relationship to recent public health controversies.
越来越多的文献表明，循环胆固醇水平与帕金森病（PD）有关。在本研究中，我们调查了胆固醇与PD之间联系的可能因果基础。
从宾夕法尼亚州立大学医学院的国立神经疾病和中风研究所（NINDS）PD生物标志物项目队列中获取了91例PD患者以及70例年龄和性别匹配的对照者的空腹血浆胆固醇水平。基于文献，选择特定胆固醇管理基因（APOE、LDLR、LRP1和LRPAP1）中的基因多态性作为混杂变量，因为它们可能同时影响胆固醇水平和PD风险。首先，应用边际结构模型，使用线性回归估计总胆固醇和低密度脂蛋白胆固醇水平与基因多态性、他汀类药物使用情况和吸烟史之间的关联。然后，在第二步中使用广义倾向评分方法研究总胆固醇和低密度脂蛋白胆固醇对PD发生的潜在因果影响。
他汀类药物（<0.001）和LRP1（<0.03）均影响总胆固醇和低密度脂蛋白胆固醇水平。APOE也有影响总胆固醇和低密度脂蛋白胆固醇的趋势（两者均为=0.08），LRPAR1有影响低密度脂蛋白胆固醇的趋势（=0.05）。相反，LDLR不影响血浆胆固醇水平（>0.19）。基于倾向评分方法，较低的总胆固醇和低密度脂蛋白胆固醇与PD显著相关（分别为<0.001和=0.04）。
当前研究表明，循环总胆固醇和低密度脂蛋白胆固醇水平可能与影响PD风险的因素有关。进一步研究以验证这些结果将影响我们对胆固醇作为PD风险因素的作用及其与近期公共卫生争议关系的理解。
