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

Objective: Case-control studies have not been consistent in showing association between apolipoprotein E (APOE) polymorphisms and frontotemporal lobar degeneration (FTLD), producing contradictory findings. The study objective was to define and quantify further the disease risk associated with the carriage of different APOE alleles to determine whether APOE gene polymorphism is a risk factor for FTLD.

Methods: A systematic review of all case-control studies investigating the association between the 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 (ORs) were estimated using a random effects model, and 95% confidence intervals (CIs) were calculated.

Results: Twenty-eight case-control studies met the inclusion criteria. Carriage of the ε2 allele had no effect on disease risk. On the contrary, carriage of the ε4 allele was associated with a significantly increased disease risk (ε4 carriers vs non-ε4 carriers: OR, 1.94; 95% CI, 1.43-2.64; ε4 vs ε3 allele: OR, 1.83; 95% CI, 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.

Conclusions: Our study provides evidence for an association between the APOE ε4 allele and frontotemporal lobar degeneration.