Abstract
Background: Numerous studies have indicated that there is a possible relationship between GBA variants and Parkinson's disease (PD), however, most of them focused on a few variants such as L444P, N370S. We performed a comprehensive pooled analysis to clarify the relationship between variations of GBA and the risk of PD in different racial groups.Methods: Standard meta-analysis was conducted, including generating inclusion and exclusion criteria, searching literature, extracting and analyzing data.Results: Fifty studies containing 20,267 PD patients and 24,807 controls were included. We found that variants 84insGG, IVS2+1G>A, R120W, H255Q, E326K, T369M, N370S, D409H, L444P, R496H and RecNciI increased the risk of PD in total populations (OR: 1.78–10.49; p: <0.00001, 0.00005, 0.0008, 0.005, <0.00001, 0.004, <0.00001, 0.0003, <0.00001, <0.0001, 0.0001). In subgroup analysis by ethnicity, in AJ populations, variants 84insGG, R496H, N370S increased the risk of PD (OR: 9.26–3.51; p: <0.00001, <0.0001, <0.00001). In total non-AJ populations, variants L444P, R120W, IVS2+1G>A, H255Q, N370S, D409H, RecNciI, E326K, T369M increased the risk of PD (OR: 8.66–1.89; p: <0.00001, 0.0008, 0.02, 0.005, <0.00001, 0.001, 0.0001, <0.00001, 0.002). Among the non-AJ populations, pooled analysis from five different groups were done separately. Variants L444P, N370S, H255Q, D409H, RecNciI, E326K increased risk of PD (OR: 6.52–1.84; p: <0.00001, <0.00001, 0.005, 0.005, 0.04, <0.00001) in European/West Asians while R120W and RecNciI in East Asians (OR: 14.93, 3.56; p: 0.001, 0.003). L444P increased the risk of PD in Hispanics, East Asians and Mixed populations (OR: 15.44, 12.43, 7.33; p: 0.00004, <0.00001, 0.009). Lacking of enough original studies, we failed to conduct quantitative analysis in Africa.Conclusions: Obvious racial differences were found for GBA variants in PD. 84insGG and R496H exclusively increased PD risks in AJ populations, so did L444P, R120W, IVS2+1G>A, H255Q, D409H, RecNciI, E326K, T369M in non-AJ populations. N370S increased the risk of PD in both ethnics. In non-AJ subgroup populations, N370S, H255Q, D409H, E326K exclusively increased PD risks in European/West Asians, as were R120W in East Asians. L444P increased the risk of PD in all groups in non-AJ ethnicity. These results will contribute to the future genetic screening of GBA gene in PD.
Highlights
Parkinson’s disease (PD), one of the most common progressive neurodegenerative disorders, is characterized by motor and nonmotor symptoms
A total of 3,006 publications were retrieved from all searched databases and 50 studies were included for further analysis (Figure 1)
According to the detecting methods, 17 of 50 publications sequenced all exons of GBA in participants and reported a series of variants either associated with PD or not (Supplementary Table 1)
Summary
Numerous studies have indicated that there is a possible relationship between GBA variants and Parkinson’s disease (PD), most of them focused on a few variants such as L444P, N370S. We found that variants 84insGG, IVS2+1G>A, R120W, H255Q, E326K, T369M, N370S, D409H, L444P, R496H and RecNciI increased the risk of PD in total populations (OR: 1.78–10.49; p:
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