Exposure factors and clinical characteristics associated with Parkinson's disease in GBA1 variant carriers: A Chinese GBA1-PD intrafamilial survey

Xuxiang Zhang; Yuwen Zhao; Li Jiang; Yuxuan Hu; Zhenhua Liu; Qian Xu; Chunyu Wang; Lifang Lei; Peishan Li; Zhihui Tan; Heng Wu; Lu Shen; Hong Jiang; Xinxiang Yan; Beisha Tang; Jifeng Guo

doi:10.1016/j.parkreldis.2024.107212

Exposure factors and clinical characteristics associated with Parkinson's disease in GBA1 variant carriers: A Chinese GBA1-PD intrafamilial survey

Parkinsonism Relat Disord. 2024 Nov 19:130:107212. doi: 10.1016/j.parkreldis.2024.107212. Online ahead of print.

Authors

Xuxiang Zhang¹, Yuwen Zhao¹, Li Jiang², Yuxuan Hu¹, Zhenhua Liu³, Qian Xu¹, Chunyu Wang⁴, Lifang Lei⁵, Peishan Li⁶, Zhihui Tan¹, Heng Wu², Lu Shen⁷, Hong Jiang⁸, Xinxiang Yan⁹, Beisha Tang¹⁰, Jifeng Guo¹¹

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
² Department of Neurology, & Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421000, China.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, China.
⁴ Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁵ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁶ Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China.
⁷ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, Hunan, 410008, China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Changsha, Hunan, 410008, China.
⁸ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China; Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, Hunan, 410008, China.
⁹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
¹⁰ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Neurology, & Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421000, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, Hunan, 410008, China.
¹¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, China; Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, Hunan, 410008, China. Electronic address: [email protected].

PMID: 39581168
DOI: 10.1016/j.parkreldis.2024.107212

Abstract

Introduction: Glucosylceramidase beta 1 (GBA1) mutations are a genetic risk factor for Parkinson's disease (PD), though most carriers do not develop the disease. This study aimed to identify exposure factors linked to PD in GBA1 carriers and assess clinical features and the probability of prodromal PD in non-manifesting carriers.

Methods: Data from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China was used, including 59 GBA1 non-manifesting carriers, 62 controls, and 107 GBA1-associated PD, of whom 81 were in the early stage. Exposure factors included pesticide/solvent exposure, smoking, alcohol, and tea consumption. Logistic regression assessed the association between exposure factors and PD. Clinical characteristics were evaluated using multiple scales, relevant markers were collected based on the Movement Disorders Society criteria. A naive Bayesian classifier method determined the probability of prodromal PD in GBA1 non-manifesting carriers and controls.

Results: After adjusting for sociodemographic variables, pesticide/solvent exposure was positively associated with PD in GBA1 carriers (OR 8.40; 95 % CI 2.50-28.20), while smoking was inversely associated with PD (OR 0.18; 95 % CI 0.05-0.62). Rapid eye movement sleep behavior disorder, constipation, hyposmia, and cognitive deficits were more severe in early-stage GBA1-associated PD than in carriers and controls. Clinical symptoms and the probability of prodromal PD were similar between carriers and controls.

Conclusions: PD in GBA1 carriers is closely linked to exposure factors. Early-stage GBA1-associated PD shows significant prodromal symptoms, which are not evident in carriers. The probability of prodromal PD in carriers is similar to that in controls.

Keywords: Clinical characteristics; Exposure factors; GBA1 variant carriers; Parkinson's disease.