| Objective:Dementia with Lewy bodies（DLB）is a neurodegenerative dementia second only to Alzheimer’s disease（AD）.At present,the etiology and pathogenesis of DLB are unknown,and few genetic factors have been identified.As one of the most common genetic risk factors for Parkinson’s disease（PD）,GBA variants increases the risk of PD.GBA variants is closely related to the formation of α-synuclein.Based on the similar pathological characteristics of DLB and PD,the effect of GBA variants on the development of DLB was further studied.At present,there are few existing studies in this area,and due to differences in study design,statistical methods,sample size,the research conclusions obtained are inconsistent.Therefore,it is necessary to conduct an objective and quantitative comprehensive analysis of the correlation between GBA variants and the risk of DLB.At the same time,there is no unified conclusion on the relationship between GBA variants and clinical features of DLB.Therefore,we conducted multiple systematic reviews and meta analyses with a particular focus on the age of onset,sex,and cognitive impairment.Methods:In this paper,we use Meta-analysis method to analyze the related literatures objectively and quantitatively: we searched Pubmed,Cochrane and bases databases comprehensively and systematically,assisted by manual search,to get the 2021 before 12 months.Strict inclusion and exclusion criteria were developed,data were extracted independently by two researchers and quality was assessed using the Newcastle-Ottawa Scale（NOS）.The Review manager 5.4 and Stata 15 software were used to conduct a Meta-analysis of the literature that met the quality requirements.Using odds ratio（OR）and 95% confidence interval（CI）as evaluation criteria,the correlation between GBA and the risk of DLB and the correlation between GBA and sex were calculated respectively,the mean difference（MD）was used to evaluate the differences of age and cognitive impairment between GBA carriers and non-carriers in DLB patients.The heterogeneity,sensitivity and bias of the results were analyzed.Result:A total of 14 studies were included.1.Our meta-analysis confirmed that the GBA variant rate was significantly higher in the DLB group than control group（OR=5.43>1,95%CI=[4.12,7.17,P<0.00001）.In DLB,the variant rate of L444 P,N370S and E326 K was significantly higher than the control group(L444P: OR=3.44>1,95%CI=[1.51,7.81],P=0.004;N370S:（OR=14.90>1,95% CI= [5.71,38.85],P<0.00001）;E326K（OR=3.99>1,95% CI= [2.67,5.96],P<0.00001）,but the variant rate of T369 M showed no significant difference between the groups.（OR=1.60>1,95% CI=[0.34,7.47],P=0.55）.2.GBA variant group had younger age of onset（MD=-5.71,95% CI= [-7.64,-3.79],P < 0.00001）and lower Montreal Cognitive Assessment score（MD =-2.48,95% CI =[-4.61,-0.35],P= 0.02）than GBA non-variant group in DLB patients.GBA variants do not differ between sexes in DLB patients（OR=1.60,95% CI = [0.93,2.74],P = 0.09）.Conclusion:1.GBA variants increased the risk of DLB,especially N370 S,E326K,and L444 P which are strongly associated with DLB,but T369 M was not.2.Patients harbouring GBA variants have earlier age of onset,moresevere cognitive impairment,and rapid symptom progression;however,sex is irrelevant in DLB. |
PDF Full Text Request