Updated Meta-Analysis Of The Role Of Apoe Epsilon 2/Epsilon 3/Epsilon 4 Alleles In Frontotemporal Lobar Degeneration

We performed an updated meta-analysis to assess the role of the epsilon 2/epsilon 3/epsilon 4 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 epsilon 4 was associated with increased FTLD risk in all genetic models (epsilon 4 vs. epsilon 3 allele, epsilon 4 vs. epsilon 2 allele, epsilon 4 vs epsilon 2+epsilon 3+epsilon 4 allele, epsilon 4 vs. epsilon 2+epsilon 3+epsilon 4 carrier, epsilon 4 epsilon 4 vs. epsilon 3 epsilon 3, epsilon 3 epsilon 4 vs. epsilon 3 epsilon 3, epsilon 3 epsilon 4+epsilon 4 epsilon 4 vs. epsilon 3 epsilon 3, epsilon 4 epsilon 4 vs. epsilon 3 epsilon 3+epsilon 3 epsilon 4, all P < 0.01, odds ratio [OR] > 1). Subgroup analysis revealed significant association between APOE epsilon 4 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 epsilon 2 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 epsilon 4 is a genetic risk factor in patients with FTLD.