Association Study Between Rs744373 Variant Of BIN1 Gene And Alzheimer’s Disease In Chinese Population

Objective: Large-scale genome-wide association studies and numerous meta-analysis indicated that the Bridging integrator1 gene was the most important susceptibility gene found in Alzheimer’s Disease(AD)following the Apolipoprotein E gene(APOE).The relationship between rs744373 variant of BIN1 gene and AD genetic risk has confirmed in European population.However,the candidate gene studies in Asian populations reported different results from European and American studies.The reasons failed to replicate the same result in Asian populations are that different ethnic background and a relatively small sample size.To further prove this point,we summarize all available studies for the association between rs744373 variant of BIN1 gene and the genetic risk of AD in Chinese population.Methods: By searching on the PubMed、CNKI、Wangfang database,all of the potential eligible studies were searched up to December 2018.We extracted the basic information for each included study to establish database.The methodological quality assessment scale was practiced to access the qualities of the included studies.This meta-analysis calculated OR、95%CI、P value by using a Peto Mantel-Haenszel fixed-effect model or a Dersimonian-Laird random-effect model to evaluate the association.We evaluated the stability of the overall results by sensitivity analysis which the removal of the included studies one by one.A Q test was performed to evaluate the heterogeneity among the selected studies.Funnel plots,Begg’s test and Egger’s linear regression were performed to examine publication bias.Results: In detail,the meta-analysis included 3,152 AD patients and 3,729 cognitive healthy controls from 11 studies.We found that the study of Jiao et al.deviated from the Hardy–Weinberg equilibrium,and the study also significantly increased the heterogeneity,but did not affect the results.Our results suggested that there may be no significant correlation between rs744373 single nucleotide polymorphism G allele gene and AD susceptibility in Chinese population.The result of stratified analysis based on the status of APOE ?4 showed that there was no significant association between the single nucleotide polymorphism of BIN1 gene rs744373 and the genetic risk of AD in APOE ?4 positive population in five genetic models.According to the different regions of population distribution,the study was divided into two sub-groups: Southerners and Northerners.In the five genetic models,no convincing correlation between rs744373 variant of BIN1 gene and AD risk was found among Southerners and Northerners.Furthermore,subgroup analysis was preformed based on the different sources of the control group.The result demonstrated that there was no significant association between BIN1 gene rs744373 variant and genetic risk of AD.However,we found in the allele model,rs744373 variant of BIN1 gene tended to increase the genetic risk of AD in the hospital-based subgroup of the control population(OR=1.09,95%CI 0.99-1.21,P=0.08).Conclusion: Although large-scale genome-wide studies have showed that the BIN1 gene is a risk gene for AD in European populations,our results indicated that there was no convincing correlation between rs744373 variant of BIN1 gene and AD risk in Chinese population.