Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Alzheimer Dis Assoc Disord. 2013 Jul-Sep;27(3):250-7. doi: 10.1097/WAD.0b013e31826d7281.
Recent genome-wide association studies (GWAS) have discovered several Alzheimer disease (AD) susceptibility loci. However, the identified susceptibility loci are substantially inconsistent across GWAS. We aimed to investigate the association of top associated variants in GWAS with AD in Korean population. We selected 86 single-nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) and genotyped in 290 AD cases and 554 unrelated controls from the same region. Three SNPs [rs429358 in APOE: odds ratio (OR)=4.24, 95% confidence interval (CI)=3.01-5.96, P=1.23×10; rs2075650 in APOE: OR=3.57, 95% CI=2.51-5.06, P=1.23×10; and rs677909 in PICALM: OR=0.63, 95% CI=0.49-0.81, P=0.00036, log additive model] were significantly associated with AD susceptibility after correction for multiple testing. Six additional PICALM SNPs, 3 ABCA7 SNPs, and 1 APOE, CD33, and BIN1 SNPs each had significant uncorrected P values. There was no significant association for age at onset of AD. Our results confirm the association of PICALM gene (encoding phosphatidylinositol-binding protein) in addition to APOE gene with AD susceptibility in Korean population but did not show significant associations of other susceptibility loci with AD.
最近的全基因组关联研究（GWAS）发现了几个阿尔茨海默病（AD）易感性位点。然而，在 GWAS 中鉴定的易感性位点在很大程度上不一致。我们旨在研究 GWAS 中与 AD 相关的顶级关联变体与韩国人群 AD 的关联。我们从 12 个基因（ABCA7、APOE、BIN1、CD2AP、CD33、CLU、CR1、EPHA1、LRAT、MS4A6A、PCDH11X 和 PICALM）中选择了 86 个单核苷酸多态性（SNP），并对来自同一地区的 290 例 AD 病例和 554 例无关对照进行了基因分型。三个 SNP [APOE 中的 rs429358：比值比（OR）=4.24，95%置信区间（CI）=3.01-5.96，P=1.23×10；APOE 中的 rs2075650：OR=3.57，95%CI=2.51-5.06，P=1.23×10；PICALM 中的 rs677909：OR=0.63，95%CI=0.49-0.81，P=0.00036，对数加性模型]在经过多重检验校正后与 AD 易感性显著相关。另外还有 6 个 PICALM SNP、3 个 ABCA7 SNP 和 1 个 APOE、CD33 和 BIN1 SNP 各自具有显著的未校正 P 值。AD 发病年龄没有显著相关性。我们的结果证实了 PICALM 基因（编码磷酸肌醇结合蛋白）除 APOE 基因外，与韩国人群 AD 易感性相关，但其他易感性位点与 AD 无显著相关性。
