Association of PSEN1 rs165932 polymorphism with Alzheimer's disease susceptibility: An extensive meta-analysis

Background: Mutations in the PSEN1 gene were found to be a causative factor with familial EOAD and PSEN1 genetic variations have the ability to alter APP metabolism. Numerous epidemiological, case-control studies have been conducted to identify the risk association between PSEN1 gene polymorphisms and Alzheimer's disease susceptibility. However, these results remain controversial. Methods: A systematic meta-analysis was performed based on previously published (Thirty seven) studies involving 12,059 participants to determine the association of rs165932 polymorphism with AD by calculating their pooled odds ratio and 95% confidence intervals under allelic, homozygote, heterozygote, dominant and recessive genetic models. Further, the publication bias was assessed by Begg's funnel plot, Egger's linear regression test and to measure the robustness of our meta-analysis, sensitivity test based on Leave one out method was also performed. Results: The analysis of rs165932 (G/T) polymorphism showed no significant association with AD risk in Caucasian, Asian and mixed ethnic populations under five genetic models. Overall, the meta-analysis demonstrated that rs165932 intronic polymorphism do not contribute to Alzheimer's disease susceptibility. Conclusions: Large-scale case-control studies from multiple ethnic populations are needed for better understanding of PSEN1 gene polymorphisms in disease pathogenesis.