Cui Shi-Shuang, Wu Ling-Yu, Li Gen, Du Juan-Juan, Huang Pei, Liu Jin, Ling Yun, Ren Kang, Chen Zhong-Lue, Chen Sheng-Di
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Parkinsons Dis. 2022 Sep 17;2022:3481102. doi: 10.1155/2022/3481102. eCollection 2022.
Genetic factors play an important role in Parkinson's disease (PD) risk. However, the genetic contribution to progression in Chinese PD patients has rarely been studied. This study investigated genetic associations with progression based on 30 PD risk loci common in a longitudinal cohort of Chinese PD patients and the Parkinson's Progression Markers Initiative (PPMI) cohort.
PD patients from the true world (TW) Chinese PD longitudinal cohort and the PPMI cohort with demographic information and assessment scales were assessed. A panel containing 30 PD risk single nucleotide polymorphisms was tested. Progression rates of each scale were derived from random-effect slope values of mixed-effects regression models. Progression rates of multiple assessments were combined by using principal component analysis (PCA) to derive scores for composite, motor, and nonmotor progression. The association of genetic polymorphism and separate scales or PCA progression was analysed via linear regression.
In the Chinese PD cohort, rs1799836 was associated with progression based on the Montreal Cognitive Assessment, the top 3 principal components (PCs) of nonmotor PCA and PC1 of the composite PCA. In the PPMI cohort, both MDS-Unified Parkinson's Disease Rating Scale II and motor PC1 progression were associated with rs12456492. The haplotype was associated with Geriatric Depression Scale and the State-Trait Anxiety Inventory for Adults progression, and the haplotype was associated with the Hoehn-Yahr staging progression and motor PC1 progression. Ethnicity-stratified analysis showed that the association between rs1799836 and PD progression may be specific to Asian or Chinese patients.
rs1799836 was associated with the progression of nonmotor symptoms, especially cognitive impairment, and the composite progression of motor and nonmotor symptoms within our Chinese PD cohort. The rs12456492 and haplotypes were associated with motor function decline, and the haplotype was associated with progression in mood in the PPMI cohort.
遗传因素在帕金森病（PD）风险中起重要作用。然而，遗传因素对中国PD患者病情进展的影响鲜有研究。本研究基于中国PD患者纵向队列和帕金森病进展标志物计划（PPMI）队列中常见的30个PD风险位点，调查了与病情进展的遗传关联。
对来自真实世界（TW）中国PD纵向队列和PPMI队列的PD患者进行人口统计学信息和评估量表评估。检测包含30个PD风险单核苷酸多态性的基因panel。各量表的进展率来自混合效应回归模型的随机效应斜率值。通过主成分分析（PCA）合并多次评估的进展率，得出综合、运动和非运动进展的评分。通过线性回归分析基因多态性与各独立量表或PCA进展的关联。
在中国PD队列中，rs1799836与基于蒙特利尔认知评估、非运动PCA的前3个主成分（PC）以及综合PCA的PC1的病情进展相关。在PPMI队列中，MDS统一帕金森病评定量表II和运动PC1进展均与rs12456492相关。单倍型与老年抑郁量表和成人状态-特质焦虑量表进展相关，单倍型与Hoehn-Yahr分期进展和运动PC1进展相关。种族分层分析表明，rs1799836与PD进展之间的关联可能特定于亚洲或中国患者。
rs1799836与中国PD队列中非运动症状的进展相关，尤其是认知障碍，以及运动和非运动症状的综合进展。rs12456492和单倍型与运动功能下降相关，单倍型与PPMI队列中的情绪进展相关。
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