John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, UK
Wellcome Trust Medical Research Council - Cambridge Stem Cell Institute, Cambridge, UK.
J Neurol Neurosurg Psychiatry. 2020 Jul;91(7):695-702. doi: 10.1136/jnnp-2020-322857. Epub 2020 Apr 17.
Variants in the gene have been identified as a common risk factor for Parkinson's disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of 'non-pathogenic' variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of 'non-pathogenic' variants on PD course is less clear. In this study, we report the effect of variants in incident PD patients with long-term follow-up.
The study population consisted of patients in the Cambridgeshire Incidence of Parkinson's disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of 'non-pathogenic' variants and carriers of pathogenic mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of variants on these outcome measures.
variants were identified in 14.4% of patients. Pathogenic and 'non-pathogenic' variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia.
variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course.
基因中的变异已被确定为帕金森病（PD）的常见风险因素。除了致病性突变（与戈谢病相关的突变）外，许多“非致病性”变异在 PD 中也以较高的频率发生。先前的研究报告称，致病性变异会对 PD 的临床病程产生不利影响。“非致病性”变异对 PD 病程的作用尚不清楚。在这项研究中，我们报告了具有长期随访的新发 PD 患者中 变异的作用。
研究人群包括来自剑桥郡普通实践到神经病学家和帕金森病：发病率、认知和剑桥郡队列中非运动障碍异质性的帕金森病的剑桥郡发病中的患者。患者分为非携带者、“非致病性”变异携带者和致病性 变异携带者。对痴呆、姿势不稳和死亡的发展时间进行生存分析。使用 Cox 回归分析控制潜在混杂因素，以确定 变异对这些结局的影响。
在 14.4%的患者中发现了 变异。致病性和“非致病性”变异与痴呆的加速发展和更具侵袭性的运动过程有关。与非携带者相比，致病性 变异与死亡率的提前有关，而与痴呆的发展无关。
包括与戈谢病无关的 变异在内的 变异在 PD 中很常见，导致更具侵袭性的疾病过程。
