Zhu Ruixia, Liu Xu, He Zhiyi
Department of Neurology, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, China.
Mol Neurobiol. 2017 Mar;54(2):1419-1428. doi: 10.1007/s12035-016-9760-2. Epub 2016 Feb 4.
Recent genome-wide association studies have identified an association between the bridging integrator 1 gene (BIN1) rs744373 polymorphism and late-onset Alzheimer's disease (LOAD) in individuals of European ancestry. Additionally, a number of studies have focused on the association between rs744373 and Alzheimer's disease in Caucasian and East Asian populations. However, these results remain inconclusive because of the relatively small sample sizes investigated. Here, we reevaluated this association using samples from seven articles including 22 independent studies comprising 11,832 LOAD patients and 18,133 controls identified by searching PubMed, MEDLINE, and AlzGene databases up to December 2015. We observed no significant heterogeneity between Asian and Caucasian populations. Additive, dominant, and recessive models revealed a significant association between rs744373 and LOAD in the pooled population, while subgroup analysis also identified significant findings in the East Asian population under the additive model (odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.19, P = 0.01) and dominant model (OR = 1.13, 95 % CI 1.03-1.25, P = 0.01), but not under the recessive model. The current meta-analysis further supports previous findings that the rs744373 polymorphism may be associated with LOAD risk in Caucasian and Asian populations. To our knowledge, this is the first large meta-analysis to investigate the association between the rs744373 polymorphism and LOAD in East Asian, American, and European populations.
近期全基因组关联研究已确定，在欧洲血统个体中，桥连整合器1基因（BIN1）rs744373多态性与晚发型阿尔茨海默病（LOAD）之间存在关联。此外，一些研究聚焦于白种人和东亚人群中rs744373与阿尔茨海默病的关联。然而，由于所调查的样本量相对较小，这些结果仍无定论。在此，我们通过检索截至2015年12月的PubMed、MEDLINE和AlzGene数据库，从七篇文章的样本中重新评估了这种关联，这些样本包括22项独立研究，涵盖11832例LOAD患者和18133例对照。我们观察到亚洲和白种人群之间无显著异质性。相加、显性和隐性模型显示，在合并人群中rs744373与LOAD之间存在显著关联，而亚组分析也在东亚人群中相加模型（优势比（OR）=1.10，95%置信区间（CI）1.02 - 1.19，P = 0.01）和显性模型（OR = 1.13，95% CI 1.03 - 1.25，P = 0.01）下发现了显著结果，但在隐性模型下未发现。当前的荟萃分析进一步支持了先前的研究结果，即rs744373多态性可能与白种人和亚洲人群的LOAD风险相关。据我们所知，这是首次在东亚、美国和欧洲人群中调查rs744373多态性与LOAD之间关联的大型荟萃分析。
