A Meta-Analysis of GBA-Related Clinical Symptoms in Parkinson’s Disease

Abstract

Background GBA gene had been proved to be a crucial gene to the risk of PD. Numerous studies had discussed about the unique clinical characteristics of PD patients with GBA carriers (GBA + PD). However, there was lack of updated comprehensive analysis on the topic. In order to clarify the association between GBA variants and the clinical phenotypes of PD, we conducted this comprehensive meta-analysis. Method Medline, Embase, and Cochrane were used to perform the searching. Strict selection criteria were followed in screening for new published articles or data. Revman 5.3 software was applied to perform the total statistical analysis, and funnel plots in the software were used to assess the publication biases. Results A total of 26 articles including 931 GBA + PD and 14861 GBA noncarriers of PD (GBA − PD) were involved in the final meta-analysis, and 14 of them were either newly added publications or related data newly analyzed compared with the version published in 2015. Then, a series of symptoms containing depression, orthostatic hypotension, motor fluctuation, wearing-off, and freezing were newly analyzed due to more articles eligible. Besides, clinical features like family history, AAO, UPDRS-III, H-Y, and dementia previously analyzed were updated with new data added. Significant statistical differences were found in wearing-off, family history, AAO, UPDRS-III, and dementia (OR: 1.14, 1.65; MD: −3.61, 2.17; OR: 2.44; p: 0.03, <0.00001, <0.00001, 0.003, and <0.00001). Depression was slightly associated with GBA + PD (OR: 1.47; p: 0.04). Clinical symptoms such as H-Y, orthostatic hypotension, motor fluctuation, and freezing did not feature GBA + PD. Conclusion Our results demonstrated that there were unique clinical features in GBA + PD which can help the management of the whole duration of PD patients.

Glucocerebrosidase Defects as a Major Risk Factor for Parkinson’s Disease

“…R496H and 84insGG increase PD risks exclusively in AJ populations, while L444P, E326K, T369M, R120W, IVS2 + 1G > A, H255Q, D409H, and RecNciI were found more frequently in non-AJ subjects. N370S is correlated to an increased PD risk in all populations (Zhang et al, 2018b).…”

“…More than 300 mutations in the GBA1 gene, such as insertions, deletions, and point mutations, have been discovered so far (O'Regan et al, 2017;Zhang et al, 2018a). The N370S (c.1226A > G) and the L444P (c.1448T > C) mutations are the most common mutations worldwide (Zhang et al, 2018b). A recent meta-analysis described other GBA1 variants, such as R120W, IVS2 + 1G > A, H255Q, D409H, RecNciI, E326K, and T369M related to PD risk.…”

GBA‐Related Parkinson's Disease: Dissection of Genotype–Phenotype Correlates in a Large Italian Cohort

“…[1][2][3][4][5] Overall, 5% to 10% of patients with PD carry a heterozygous GBA variant, but such frequency varies widely among populations, from 10% to 31% in Ashkenazi Jewish to 3% to 12% in non-Jewish cohorts, and 2.8% to 4.5% in Italy. [5][6][7][8][9][10][11] However, most studies have only tested the most common GBA mutations, likely underestimating prevalence rates. To date, more than 500 pathogenic variants have been reported and classified as complex, severe, and mild based on the mutation type and residual GCase activity in patients with Gaucher disease (GD).…”

Parkinson’s disease in Gaucher disease patients: what’s changing in the counseling and management of patients and their relatives?

“…The important role of GBA1 in the pathogenesis of PD was firmly established when larger populations of PD patients were screened worldwide [ 14 ]. Several studies confirmed the significantly higher incidence of GBA1 mutations among PD patients compared to non-affected subjects in various populations [ 15 ].…”