Apolipoprotein E polymorphisms in frontotemporal lobar degeneration: A meta-analysis.

Background: Case-control studies have not been consistent in showing association between APOE polymorphisms and FTLD, producing contradictory findings. Objective: To further define and quantify the disease risk associated with the carriage of different APOE alleles, in order to determine if APOE gene polymorphism is a risk factor for FTLD. Methods: A systematic review for all case-control studies investigating the association between APOE gene and FTLD up to December 2011 was conducted. Case-control studies using clinical or pathological criteria for FTLD and reporting APOE allelic or genotypic data were included. Pooled odds ratios (OR) were estimated using random effects (RE) model, and 95% Confidence Intervals (CIs) were calculated. Results: 28 case-control studies met the inclusion criteria. The carriage of the ε2 allele had no effect on the disease risk. On the contrary, the carriage of the ε4 allele was associated with a significantly increased disease risk (ε4 carriers vs non ε4 carriers (OR 1.94; C.I. 95% 1.43-2.64; ε4 vs ε3 allele: OR 1.83; C.I. 95% 1.34-2.52). Furthermore, a gene-dosage effect for the ε4 allele was found. There was no evidence of publication bias, but heterogeneity between the studies was high. Conclusion: Our study provides evidence for an association between the APOE ε4 allele and Frontotemporal Lobar Degeneration.