Risk Analysis Of GBA Gene Mutation L444P On The Pathogenesis Of Parkinson’s Disease

Objectives:Parkinson’s Disease(PD)is a neurodegenerative disorder that includes motor symptoms such as tremor,rigidity,bradykinesia and postural instability and non-motor symptoms such as sensory dysfunction,sleeping dysfunction,autonomic dysfunction,and mental dysfunction.PD is the second most frequent neurodegenerative disease after Alzheimer’s disease.The global incidence rate is 8-18 cases per 100,000 people per year,and the incidence rate in male is higher than that in female.The pathogenesis of Parkinson’s disease includes genetic factors,environmental factors,aging of the nervous system and the interaction of multiple factors.Due to the atypical symptoms of its early onset,delays in seeking medical attention because of patients’ neglect to prodromal symptoms and the specific biomarkers for the diagnosis of PD has not yet been found caused many patients to be unable to receive timely diagnosis and treatment.Therefore,the identification of genes that cause Parkinson’s disease susceptibility will be of great significance for the early detection and treatment of Parkinson’s disease.GBA gene mutations are currently considered to be related to the risk of PD.Among them,there are more studies on the mutation L444 P.We assessed the relationship between L444 P and the risk of Parkinson’s disease through meta-analysis,and divided it into multiple subgroups to analyze the difference between various areas.Methods:Through a comprehensive and systematic search of "glucocerebrosidase","Parkinson’s disease" in Pubmed,Web of Science,EMbase,Cochrane and Books@Ovid,the literature on all cross-sectional study published on the “GBA gene for the risk of Parkinson’s disease”published from January 1,2005 to November 30,2020,developed strict inclusion and exclusion criteria,and two researchers independently screened the literature.Quality evaluation,data extraction,odds ratio(OR)as effect statistics,Meta-analysis of data using Stata14.0.Results:The risk of Parkinson’s disease in the mixed population carrying L444 P is 8.887 times that of non-carriers(OR=8.887,95% CI4.016～19.667);the risk of Parkinson’s disease in the Asian population carrying L444 P is 12.594 times that of non-carriers(OR=12.594,95% CI3.822～41.493);the risk of Parkinson’s disease in European population carrying L444 P is 4.976 times that of non-carriers(OR = 4.976,95% CI1.282-19.313);the risk of Parkinson’s disease in the Brazilian population carrying L444 P is 11.189 times that of non-carriers(OR=11.189,95% CI1.245～100.585).Conclusion:1.GBA gene mutation subtype L444 P can increase the risk of Parkinson’s disease in mixed populations;2.Compared with the European population and the Brazilian population,the mutation L444 P increases more risk of Parkinson’s disease in East Asian populations.