Su Wen-Hua, Shi Zhi-Hong, Liu Shu-Ling, Wang Xiao-Dan, Liu Shuai, Ji Yong
Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China.
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China.
Oncotarget. 2017 Jul 4;8(27):43721-43732. doi: 10.18632/oncotarget.17341.
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.
我们进行了一项更新的荟萃分析，以评估载脂蛋白E基因（APOE）的ε2/ε3/ε4等位基因在额颞叶变性（FTLD）中的作用。从PubMed、CENTRAL、EMBASE和Web of Science数据库中检索相关文章，并根据纳入和排除标准进行筛选后，选择了51项符合条件的病例对照研究，其中包括5123例病例和20566例对照。我们的分析表明，在所有遗传模型中，APOE ε4与FTLD风险增加相关（ε4与ε3等位基因、ε4与ε2等位基因、ε4与ε2+ε3+ε4等位基因、ε4与ε2+ε3+ε4携带者、ε4ε4与ε3ε3、ε3ε4与ε3ε3、ε3ε4+ε4ε4与ε3ε3、ε4ε4与ε3ε3+ε3ε4，所有P<0.01，比值比[OR]>1）。亚组分析显示，对于白种人、意大利人、基于人群（PB）、哈迪-温伯格平衡（HWE）的P>0.05值、纽卡斯尔-渥太华量表评分>6以及行为变异型额颞叶痴呆（bvFTD）亚组，APOE ε4与FTLD之间存在显著关联（P<0.01，OR>1）。然而，在大多数遗传模型和亚组分析中，APOE ε2等位基因与FTLD之间无显著关联（P>0.05）。Begg检验和Egger检验也未显示发表偏倚，敏感性分析表明我们的数据分析具有稳健性。因此，我们的荟萃分析表明，APOE ε4是FTLD患者的一个遗传危险因素。
