Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
Parkinsonism Relat Disord. 2011 Feb;17(2):84-8. doi: 10.1016/j.parkreldis.2010.11.011. Epub 2010 Dec 16.
Parkinson's disease (PD) is a complex neurodegenerative disorder contributed by both environmental and genetic factors. The inconsistent findings in genetic association studies may be due to unrecognized interactions with other genetic or environmental factors. Therefore, we assessed the combined effects of genetic variants of three candidate genes of familial PD and environmental exposure on risk of PD in Taiwanese population. A total of 744 study subjects, 453 PD cases and 291 ethnicity-matched controls, were included. The genetic variants on the PINK1, BDNF, and LRRK2 genes were sequenced accordingly. We used a regression approach based on a generalized linear model to evaluate single-locus genotype effects and detection of gene-environment interaction by incorporating interaction terms in the model. We found a significant difference of LRRK2 G2385R and R1628P between PD patients and controls, which confirmed our previous findings. A logistic regression model which included gene-environment interactions was applied. Notably, we identified the variant of LRRK2 T4939A (S1647T) (TT, OR = -0.36, p = 0.03) is associated with increased PD risk, after considering the interaction effects with environmental factors in the model. Additionally, two novel interactions were detected: pesticide exposure with BDNF (OR = -0.85, p = 0.01) and to a lesser extent, with PINK1 (OR = 1.99, p = 0.07). Our findings reinforced the importance that PD risk is modulated by both genetic and environmental exposures. LRRK2 S1647T may be another risk factor for PD development in our ethnicity while considering the joint interaction effects with environmental factors.
帕金森病（PD）是一种复杂的神经退行性疾病，由环境和遗传因素共同作用引起。遗传关联研究中的不一致发现可能是由于与其他遗传或环境因素未被识别的相互作用所致。因此，我们评估了三个家族性 PD 候选基因的遗传变异与环境暴露在台湾人群中对 PD 风险的综合影响。共纳入 744 例研究对象，其中 453 例为 PD 病例，291 例为匹配的对照组。相应地对 PINK1、BDNF 和 LRRK2 基因的遗传变异进行了测序。我们使用基于广义线性模型的回归方法来评估单基因座基因型的影响，并通过在模型中纳入交互项来检测基因-环境相互作用。我们发现 PD 患者和对照组之间 LRRK2 G2385R 和 R1628P 的差异有统计学意义，这证实了我们之前的发现。应用了包含基因-环境相互作用的逻辑回归模型。值得注意的是，我们发现 LRRK2 T4939A（S1647T）（TT 基因型，OR = -0.36，p = 0.03）变体与环境因素的交互作用考虑在模型中后，与 PD 风险增加相关。此外，还检测到两个新的相互作用：农药暴露与 BDNF（OR = -0.85，p = 0.01），以及与 PINK1 的相互作用较弱（OR = 1.99，p = 0.07）。我们的研究结果强调了 PD 风险是由遗传和环境暴露共同调节的。在考虑与环境因素的联合交互作用时，LRRK2 S1647T 可能是我们人群中 PD 发展的另一个危险因素。
