Wen Liu, Yinlian Han, Yuqian Liu, Min Tian, Heyin Liu, Yang Yang, Jinde Liu, Chengyuan Song, Yiming Liu
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引用次数: 0
Abstract
Backgroud: Orthostatic hypotension (OH) is not rare in patients with Parkinson's disease (PD). To date, there have been few studies on the association of genetic variants with OH.
Objectives: We aimed to evaluate the association of LRRK2 and GBA variants with OH in a large PD cohort.
Methods: This study utilized data from the PPMI database, including 863 participants who were divided into the sporadic PD patients (sPD, n = 357), GBA variant carriers (GBA-PD, n = 137), LRRK2 variant carriers (LRRK2-PD, n = 158) and healthy controls (HC, n = 211). LRRK2-PD patients were additionally categorized into G2019S (n = 141) and R1441G (n = 16). GBA-PD patients were categorized into three subgroups by the genomic categorization.
Results: No significant difference was found in the incidence of OH among the four groups at baseline. Lower University of Pennsylvania Scent Identification Test (UPSIT) scores, higher Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score and the risk GBA mutations were significantly associated with OH cross-sectionally. Higher Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total and part II scores, higher Epworth Sleepiness Scale (ESS) scores, higher RBDSQ scores and higher Scales for Outcomes in Parkinson's Disease-Autonomic Questionnaire (SCOPA-AUT) scores were strongly linked with OH progression over time. LRRK2 mutations especially LRRK2 G2019S mutation were significantly associated with the lower risk of OH progression.
Conclusion: LRRK2-PD, particularly the LRRK2-G2019S-PD, were found to have a lower risk of OH. In contrast, the role of GBA mutations in OH appears more complex, with no further evidence to suggest that GBA is associated with the progression of OH in PD.
背景：直立性低血压（OH）在帕金森病（PD）患者中并不罕见。迄今为止，很少有关于基因变异与OH之间关系的研究。目的：我们旨在评估大型PD队列中LRRK2和GBA变异与OH的关系。方法：本研究利用PPMI数据库的数据，纳入863名参与者，分为散发性PD患者（sPD, n = 357）、GBA变异携带者（GBA-PD, n = 137）、LRRK2变异携带者（LRRK2-PD, n = 158）和健康对照组（HC, n = 211）。LRRK2-PD患者另外分为G2019S （n = 141）和R1441G （n = 16）。根据基因组分类，将GBA-PD患者分为三个亚组。结果：四组患者在基线时OH发生率无显著差异。宾夕法尼亚大学气味识别测试（UPSIT）得分较低，快速眼动睡眠行为障碍筛查问卷（RBDSQ）得分较高，GBA突变风险与OH呈横断性显著相关。较高的运动障碍学会统一帕金森病评定量表（MDS-UPDRS）总分和第二部分评分、较高的Epworth嗜睡量表（ESS）评分、较高的RBDSQ评分和较高的帕金森病结局量表（SCOPA-AUT）评分与OH随时间的进展密切相关。LRRK2突变，特别是LRRK2 G2019S突变与OH进展风险降低显著相关。结论：LRRK2-PD，特别是LRRK2-G2019S-PD具有较低的OH风险。相比之下，GBA突变在OH中的作用似乎更为复杂，没有进一步的证据表明GBA与PD中OH的进展有关。
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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