Risk Analysis Of GBA Gene Polymorphism And Gene Mutation On The Pathogenesis Of Parkinson's Disease Dementia:A Meta-analysis

Objectives:Parkinson's Disease Dementia(PDD)is a common and severe non-motor symptom of Parkinson's disease.The cumulative prevalence of Parkinson's disease in patients with a disease duration of more than 10 years is 75-90%,giving patients family and society a heavy burden.Gene factors play an important role in the pathogenesis of Parkinson's disease dementia.Searching for genes associated with Parkinson's disease dementia is of great significance for the early diagnosis and treatment of Parkinson's disease dementia.The glucocerebrosidase(GBA)gene is the most common genes associated with Parkinson's disease in the population,whether GBA gene polymorphisms and gene mutations increase the risk of Parkinson's disease dementia remains controversial.We performed a meta-analysis to assess the risk of GBA gene polymorphisms and gene mutations in the pathogenesis of Parkinson's disease dementia,with a view to clarifying the relationship between GBA genotype and Parkinson's disease dementia.Methods:Through a comprehensive and systematic search of "glucocerebrosidase","Parkinson's disease" and "dementia" in Pubmed,Coc HRane,Embase,CBM,CNKI,China Knowledge Network,Wanfang database,the literature on all case-control studies and cohort studies published on the “GBA gene for the risk of Parkinson's disease dementia” published before September 30,2018,developed strict inclusion and exclusion criteria,and two researchers independently screened the literature.Quality evaluation,data extraction,ln(HR)and seln(HR)as effect statistics,Meta-analysis of data using Stata12.0.Results:The risk of Parkinson's disease dementia in GBA gene variant carriers is 1.94 times that of non-carriers(HR=1.94,95% CI 1.53~2.46);the risk of dementia in Parkinson's disease patients with GBA gene polymorphism is non-carrier 1.87 times(HR=1.87,95% CI1.18~2.98);the risk of dementia in patients with Parkinson's disease carrying GBA mutation was 3.64 times that of non-carriers(HR=3.64,95% CI 2.74~2.83),GBA mutationN370 S Parkinson's disease patients with dementia risk ratio(HR)was 1.95(HR=1.95,95%CI 1.29~1.94),L444 P dementia risk ratio(HR)was 4.81(HR=4.81,95 %CI is 3.37~6.86),which is significantly higher than N370 S.Conclusion:Patients with Parkinson's disease carry GBA gene polymorphism,GBA gene mutation is higher than non-carriers with high risk of dementia,GBA gene polymorphism,GBA gene mutation is a possible risk factor for Parkinson's disease dementia;Parkinson's disease patients carry mutation gene N370 S and L444 P have higher risk of dementia than non-carrier Parkinson's disease.N370 S and L444 P are risk factors for Parkinson's disease dementia.L444 P is more risky than N370 S Parkinson's disease dementia;The risk of Parkinson's disease dementia with GBA gene mutation in Japan population is higher than in European population.