Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
Department of Human Genetics and Biomathematics, UCLA David Geffen School of Medicine, Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, USA.
Parkinsonism Relat Disord. 2019 May;62:57-61. doi: 10.1016/j.parkreldis.2019.01.031. Epub 2019 Feb 1.
Negative associations between smoking and Parkinson's disease (PD) are well documented. While common biases may not explain this association, some studies have suggested reverse causality and ease of quitting might be an early sign of PD, possibly related to a reduced nicotinic response. We investigated nicotinic receptor (nAChR) genetics to add to our understanding of possible biologic mechanisms underlying the smoking-PD relationship.
We relied on 612 patients and 691 controls enrolled in the PEG (Parkinson's Environment and Gene) study for whom we obtained information on smoking and quitting ease through interviews. Genotyping in the nAChR genes, i.e. CHRNA5-A3-B4 and CHRNB3-A6 gene regions that have been linked to smoking or quitting behaviors, were based on blood and saliva DNA samples. We assessed associations with logistic regression assuming logit-additive allelic effects and used product terms for genetic allele status and smoking or quitting assessing interactions.
As expected, we observed negative associations between smoking and PD that were strongest for current followed by former smokers. In former smokers, high quitting difficulty was negatively associated with PD risk (extremely hard vs. easy: OR = 0.62 [0.39-0.99], p = 0.05), meaning those who developed PD were able to quit smoking with less difficulty than controls. The CHRNA3 rs578776-A allele predicted quitting difficulty in smoking controls (OR = 0.53 [0.32-0.91], p = 0.02), but not in smoking PD patients (OR = 1.09 [0.61-1.95], p = 0.77).
Our study further corroborates previous findings that ease of quitting may be an early sign of PD onset related to a loss of nicotinic response in prodromal stages.
吸烟与帕金森病（PD）之间存在负相关关系，这一点已有充分的文献记载。虽然常见的偏倚可能无法解释这种关联，但一些研究表明，反向因果关系和戒烟的容易程度可能是 PD 的早期迹象，这可能与尼古丁反应减少有关。我们研究了尼古丁受体（nAChR）的遗传学，以进一步了解吸烟与 PD 之间关系的潜在生物学机制。
我们依赖于参加 PEG（帕金森环境与基因）研究的 612 名患者和 691 名对照者，通过访谈获得了有关吸烟和戒烟难易程度的信息。nAChR 基因（即与吸烟或戒烟行为相关的 CHRNA5-A3-B4 和 CHRNB3-A6 基因区域）的基因分型基于血液和唾液 DNA 样本。我们使用逻辑回归来评估与假设的对数加性等位基因效应相关的关联，并使用遗传等位基因状态和吸烟或戒烟的乘积项来评估相互作用。
正如预期的那样，我们观察到吸烟与 PD 之间存在负相关关系，其中当前吸烟者和以前吸烟者的相关性最强。在以前的吸烟者中，高戒烟难度与 PD 风险呈负相关（非常困难与容易：OR=0.62 [0.39-0.99]，p=0.05），这意味着那些发展为 PD 的人比对照组更容易戒烟。CHRNA3 rs578776-A 等位基因预测吸烟对照组的戒烟难度（OR=0.53 [0.32-0.91]，p=0.02），但不能预测吸烟 PD 患者的戒烟难度（OR=1.09 [0.61-1.95]，p=0.77）。
我们的研究进一步证实了先前的发现，即戒烟的容易程度可能是 PD 发病的早期迹象，与前驱期尼古丁反应丧失有关。
