Abstract
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.
Highlights
Frontotemporal lobar degeneration (FTLD) is a common form of dementia that is characterized by focal atrophy of frontal and/or anterior temporal brain lobes [1]
In 2002, Verpillat et al [13] carried out a metaanalysis of 11 studies, and reported that Apolipoprotein E (APOE) ε2 was associated with an increased risk of FTLD in the Caucasian population
In 2013, another metaanalysis based on 28 studies by Rubino et al [14] in 2013 showed that FTLD susceptibility was associated with APOE ε4, but not ε2
Summary
Frontotemporal lobar degeneration (FTLD) is a common form of dementia that is characterized by focal atrophy of frontal and/or anterior temporal brain lobes [1]. Several genetic variants are associated with FTLD [4,5,6]. In the Italian population, C276T polymorphism of neuronal nitric oxide synthase (nNOS) gene is linked to increased susceptibility to sporadic FTLD [5]. A2518G polymorphism in monocyte chemotactic protein 1 (MCP-1) gene is a protective factor of sporadic FTLD [6]. The conclusions of various studies that have investigated the role of APOE polymorphism in FTLD have been inconsistent and contradictory. APOE ε4 was associated with increased FTLD risk in the Dutch population [9]. A negative association was reported between APOE polymorphism and FTLD risk in German patients [10]. Genome wide association studies (GWAS) data of FTLD did not confirm a positive association with the APOE gene [11, 12]
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