Updated meta-analysis of the role of APOE ε2/ε3/ε4 alleles in frontotemporal lobar degeneration

We performed an updated meta-analysis to assess the role of the ε2/ε3/ε4 alleles of Apolipoprotein E gene (APOE) in frontotemporal lobar degeneration (FTLD). The relevant articles were retrieved from PubMed, CENTRAL, EMBASE and Web of Science databases, and 51 eligible case-control studies with 5123 cases and 20566 controls were selected after screening according to inclusion and exclusion criteria. Our analysis demonstrated that APOE ε4 was associated with increased FTLD risk in all genetic models (ε4 vs. ε3 allele, ε4 vs. ε2 allele, ε4 vs. ε2+ε3+ε4 allele, ε4 vs. ε2+ε3+ε4 carrier, ε4ε4 vs. ε3ε3, ε3ε4 vs. ε3ε3, ε3ε4+ε4ε4 vs. ε3ε3, ε4ε4 vs. ε3ε3+ε3ε4, all P < 0.01, odds ratio [OR] > 1). Subgroup analysis revealed significant association between APOE ε4 and FTLD (P < 0.01, OR > 1) for the Caucasian, Italian, population based (PB), P > 0.05 value of the Hardy-Weinberg Equilibrium (HWE), Newcastle-Ottawa scale score > 6, and behavioral variant frontotemporal dementia (bvFTD) subgroups. However, there was no significant association between the APOE ε2 allele and FTLD (P > 0.05) in most genetic models and sub-group analyses. Begg's and Egger's tests also revealed no publication bias, and sensitivity analysis showed that our data analysis was robust. Thus our meta-analyses suggest that APOE ε4 is a genetic risk factor in patients with FTLD.