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

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.