title: Presenilin-2 polymorphisms and risk of sporadic AD: evidence from a meta-analysis.
abstract: Association studies of presenilin-2 (PSEN2) polymorphisms and sporadic Alzheimer's disease (AD) have yielded inconsistent results, possibly because single studies often lack sufficient statistical power. In this study, we performed a meta-analysis to evaluate the association of the two most extensively studied PSEN2 polymorphisms, rs8383 and 5'indel, with the risk of sporadic AD. We systematically reviewed relevant studies retrieved by Medline, Pubmed, Embase, AlzGene, and CNKI. Data were analyzed using the Stata (v11.0) software package. The fixed effects model or random-effects model were applied depending on between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's funnel plots. Overall, the meta-analysis included 6 case-control studies for each polymorphism with 2186 confirmed AD cases and 2507 healthy controls in total. Analysis suggested a significant association between SNP rs8383 polymorphism and AD risk with no evidence of between-study heterogeneity or publication bias. In contrast, we found no evidence for an association between the 5'indel polymorphism and AD risk. Further stratified analyses by apolipoprotein ε4 status or ethnicity also failed to reveal a statistically significant association between the 5'indel polymorphism of PSEN2 and AD risk. Our analysis supports the hypothesis that the PSEN2 rs8383 polymorphism is associated with an enlarged risk of sporadic AD. However, larger scale association studies are necessary to further validate the association of PSEN2 polymorphisms with sporadic AD risk and to define potential gene-gene interactions.
authors.affiliation: Department of Occupational Health, Faculty of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Chen
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Mingyue
authors.initials: M
authors.lastname: Qu
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D020641:Polymorphism, Single Nucleotide; D053766:Presenilin-2 / Q000235:genetics*
chemical_list: C508861:PSEN2 protein, human; D053766:Presenilin-2