Effects of glucocerebrosidase gene polymorphisms and mutations on the risk of Parkinson's disease dementia: a meta-analysis

Abstract Objective Exploring the impact of glucocerebrosidase gene (GBA) polymorphisms and mutations on the pathogenesis of Parkinson’s disease dementia (PDD) plays an important role in the diagnosis and treatment of this disease. This meta-analysis aimed to investigate the effects of GBA polymorphisms and mutations on the risk of PDD and to identify the relationship between GBA genotype and PDD. Methods A computer-based search was performed to retrieve publications from PubMed, Cochrane library, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang databases using the search terms “glucocerebrosidase”, “Parkinson’s disease”, and “dementia”. After rigorous screening, cohort studies were included for meta-analysis. Results The risk of PDD in GBA variant carriers was 1.94 times that in non-carriers (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.53–2.46). The risk of PDD in GBA polymorphism carriers was 1.87 times that in non-carriers (HR, 1.87; 95% CI, 1.18–2.98). The risk of PDD in GBA mutation carriers was 3.64 times that in non-carriers (HR, 3.64; 95% CI, 2.74–4.83). The risk of PDD in p.L444 P variant carriers (HR, 4.81; 95% CI, 3.37–6.86) was significantly higher than that in p.N370S variant carriers (HR, 1.95; 95% CI, 1.29–1.94). Conclusion GBA polymorphisms and mutations are potential risk factors for PDD.