Meta-analysis Of The Relationship Between Apolipoprotein E Gene Polymorphism And Vascular Dementia In Chinese Population

Objective: Vascular dementia (VaD) is defined as loss of cognitive function resulting from ischemic, hemorrhagic or hypoperfusive brain lesions due to cerebrovascular disease. VaD is a common cause of dementia, second in prevalence only to Alzheimer's disease. Vascular dementia and stoke are thought in general terms to share the same risk factors, commonly including hypertension, diabetes, hypercholesterolemia, smoking, myocardial infarction etc. In recent years, genetic research of VaD has received increasing attentions.Apolipoprotein E (ApoE) was first found by Shore in 1973. It is an alkaline protein which is rich of arginine. ApoE gene is localized on chromosome 19 and consists of 299 amino acids. ApoE gene shows significant genetic polymorphism. The three major isoformes (E2, E3 and E4) are the products of three alleles (ε2,ε3 andε4) and consequently produce six genotypes of different combinations of the three isoformes, including three homozygous genotypes (ε2/2,ε3/3 andε4/4) and three heterozygous genotypes (ε2/3,ε2/4 andε3/4). ApoE is a major component of plasma lipoproteins, which is mainly synthesized in liver and brain. It plays an important role both in the metabolism of plasma lipids and in the growth and repair of the nervous system during development or after injury.ApoE gene polymorphism is significantly associated with Alzheimer's disease and ApoEε4 can increase the risk of Alzheimer's disease. However the relationship between ApoE gene polymorphism and vascular dementia is still controversial. So we carried out a meta-analysis of case-control studies of sufficient rigor for the purpose of investigating the relationship between ApoE gene polymorphism and vascular dementia in Chinese population to enrich the understanding of the genetic factors in relation to the pathogenesis of vascular dementia.Methods: CNKI, Wanfang Data, Pubmed and EMCC databases were searched for related literatures published from 1998 to 2009. All studies were inclued or excluded based on the inclusion and exclusion criteria. The qualities of the eligible studies were assessed and the data were extracted for statistical analyse. Between-study heterogeneity was explored by Q test, a pooled effect was calculated with a random-effects model (REM) where between-study heterogeneity existed (P<0.05); otherwise, a fixed-effects model (FEM) was used. Sensitivity analysis was done to the results. Publication bias was assessed with funnel plots and fail-safe numbers (Nfs). Odds ratios (ORs) and its 95% CI of ApoE alleles and genotypes distributions in vascular dementia patients and healthy controls were calculated. All analyses were conducted using software RevMan 4.2.Results: Of the 78 identified studies, 8 studies were selected for statistical analysis based on the criteria and Hardy-Weinberg equilibrium testing. All the studies were case-control studies, seven published in Chinese and one in English. The total samples were 1104, 416 of VaD group and 688 of NC group. Q test showed no significant heterogeneity of ApoE alleles frequencies and genotypes frequencies between every study and all pooled effects were calculated with a fixed-effects model (FEM). Meta-analysis results indicated that the pooled ORs and 95% CIs of alleleε4 and genotypeε3/4 of ApoE gene in VaD group as compaired with NC group were 2.00[1.50, 2.65] and 2.12[1.52, 2.97](P<0.01), and the pooled ORs and 95% CIs of alleleε3 and genotypeε3/3 were 0.65[0.52, 0.82] and 0.59[0.45, 0.77](P<0.01). There were no significant differences of alleleε2 or genotypeε2/2,ε2/3,ε2/4 andε4/4 in VaD group as compaired with those in normal control. Sensitivity analysis results were similar to the original results, which proved that the conclusion of this Meta-analysis was stable and reliable. The funnel plots for ApoEε4,ε3 andε3/4,ε3/3 were all symmetrical and the fail-safe numbers were all larger than the number of the selected studies, which indicated that the publication bias were under control and the result was reliable.Conclusions: The results suggests that ApoE gene polymorphism is significantly associated with vascular dementia in Chinese population.ApoEε4 may be a risk factor andε3 may be a protective factor for VaD.