The Association Between ApoE Gene Polymorphisms And Alzheimer’s Disease In Chinese Population: A Meta-analysis

Backgroud：Alzheimer’s disease is a progressive， irreversible and multi-gene-relatedneurodegenerative disorders, which characterized by worsening cognitiveimpairment.With the rapid development of global aging population, its prevalence isalso increasing, seriously affected the physical and mental health of the elderly andthe quality of life, brings heavy burden to society and family as well. The etiologyand pathogenesis of AD are still unclear. A number of studies indicate that geneticfactor is an very important pathogenic factor of the AD, which there are three kinds ofgenes associated with early-onset familial AD, including amyloid precursor protein(APP), presenilin-1(PS-1), presenilin-2(PS-2). While the ApoE gene may beassociated with late onset familial AD and sporadic AD. ApoE gene has geneticpolymorphism. Foreign studies suggest carrying ε4is associated with the occurrenceof AD, while carrying ε2may be protective. The studies on the relationship betweenApoE gene polymorphism and AD in chinese population have been reportedsuccessively, which need to be further systematic evaluation.Objective：To systemically review the relationship between gene polymorphisms of ApoEand Alzheimer’s disease in Chinese population.Methods：By computer search PUBMED, Chinese Biomedical Literature analysis andretrieval system for compact disc (CBMdisc), Chinese Journal Full-text Database(CNKI), VIP Journals Database (VIP), Wanfang Full-text Database, combined withthe Google Scholar and literature tracing method, the literature published at home and abroad between January2003to May2013were collected comprehensively.Theprocess was completed by two researchers summarized after independence retrieval.The literature inclusion and exclusion standard were formulated strictly. Followed bythe two evaluators were to assess the the quality of the literature which were alleligible based on above criteria respectively and extract the relevant data. ApplicationRevMan5.0and Stata12.0software for Meta analysis into the results of the includedliterature: RevMan5.0were applied for evaluation the heterogeneity between studiesbased on Q test and I2statistics. According to heterogeneity test results to choosethe fixed effects model (P>0.10,and I2≤50%) or random effects model (P≤0.10,andI2>50%)for data consolidation.Then,To calculate combined statistics P value, oddsratio(OR) and95%confidence interval (CI). Sensitivity analysis was carried on thestability and reliability of the evaluation results. Drawing funnel plot, And combiningwith Stata12.0software Begg ’s and Egger’ s test to assess publication bias.Results(1) There were11qualified literatures(13studies) to research, accumulative totalof2577cases with AD group1209cases and control group1368cases. Meta analysisfound that: there were better heterogeneity exists between different research (P>0.10),so using a fixed effects model for data consolidation. The results showed thatindividuals with ApoE ε4allele and ε3/4, ε4/4genotype were increased significantlythe risk of Alzheimer’s disease[ε4vsε3: OR=2.88,95%CI(2.41,3.44); ε3/4vs ε3/3:OR=2.62,95%CI(2.11,3.25); ε4/4vs ε3/3: OR=7.98,95%CI(4.21,15.13)].Individuals with ApoE ε2allele and ε2/3genotype were decreased significantly therisk of Alzheimer’s disease[ε2vs ε3: OR=0.77,95%CI(0.62,0.96); ε2/3vs ε3/3:OR=0.76,95%CI(0.58,0.98)]. Individuals with ApoE ε2/2and ε2/4genotype wereincreased the risk of Alzheimer’s disease, but there was no statistically significantdifference [ε2/2vs ε3/3: OR=1.38,95%CI(0.57,3.37); ε2/4vs ε3/3: OR=1.21, 95%CI(0.67,2.18)].(2) Sensitivity analysis found that changing effects model analysis and excludedone by one after each study had no obvious effect on the Meta-analysis results. Theresults showed that the stability was better.(3) Each allele and genotype funnel plots showed basic symmetric visually, andBegg’s and Egger’s test also showed no significant publication bias (P>0.05). Thepresent study indicated that publication bias had been effectively controlled.ConclusionApoE gene polymorphisms are closely associated with the occurrence ofAlzheimer’s disease in Chinese population. ApoE ε4allele and ε3/4、ε4/4genotypeare risk factors for Alzheimer’s disease. ApoE ε2allele and ε2/3genotype areprotective factors for Alzheimer’s disease.