Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
Atherosclerosis. 2009 Nov;207(1):144-9. doi: 10.1016/j.atherosclerosis.2009.03.038. Epub 2009 Apr 5.
We have performed a genome-wide association study (GWAS) to identify genetic variants that confer susceptibility to ischemic stroke.
A total of 6341 individuals from three independent populations was examined. Subject panel A comprised 131 individuals with ischemic stroke and 135 controls; subject panel B comprised 790 individuals with ischemic stroke and 3435 controls; and subject panel C comprised 71 individuals with ischemic stroke and 1779 controls. A GWAS for ischemic stroke was performed in subject panel A with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).
The relation of 100 single nucleotide polymorphisms (SNPs) selected by the GWAS to ischemic stroke was examined in 705 subjects with ischemic stroke and 3426 controls selected from subject panel B. Three SNPs (rs1671021 of LLGL2, rs9615362 of CELSR1, and rs753307 of RUVBL2) were significantly (P<0.05) associated with ischemic stroke. After DNA sequencing of linkage disequilibrium blocks containing these SNPs, three tag SNPs (rs6007897 of CELSR1, rs1671021 of LLGL2, and rs1062708 of RUVBL2) and a nonsynonymous SNP (rs4044210 of CELSR1) were examined for their relation to ischemic stroke in subject panels B and C. Both rs6007897 (A-->G, Thr2268Ala) and rs4044210 (A-->G, Ile2107Val) of CELSR1 as well as rs1671021 (T-->C, Phe479Leu) of LLGL2 were significantly associated with ischemic stroke in subject panel B. The rs6007897 and rs4044210 polymorphisms of CELSR1 were also significantly associated with ischemic stroke in subject panel C.
CELSR1 is a susceptibility gene for ischemic stroke in Japanese individuals, although the functional relevance of the identified SNPs was not determined.
我们进行了一项全基因组关联研究（GWAS），以确定易患缺血性中风的遗传变异。
共检查了来自三个独立人群的 6341 个人。受试者 A 组包括 131 名缺血性中风患者和 135 名对照者；受试者 B 组包括 790 名缺血性中风患者和 3435 名对照者；受试者 C 组包括 71 名缺血性中风患者和 1779 名对照者。使用基因芯片人类图谱 500K 阵列集（Affymetrix）对受试者 A 组进行了缺血性中风的 GWAS。
GWAS 选择的 100 个单核苷酸多态性（SNP）与 705 名缺血性中风患者和从受试者 B 组中选择的 3426 名对照者的缺血性中风关系进行了检查。三个 SNP（LLGL2 的 rs1671021、CELSR1 的 rs9615362 和 RUVBL2 的 rs753307）与缺血性中风显著相关（P<0.05）。在对包含这些 SNP 的连锁不平衡块进行 DNA 测序后，在受试者 B 和 C 组中检查了三个标签 SNP（CELSR1 的 rs6007897、LLGL2 的 rs1671021 和 RUVBL2 的 rs1062708）和一个非同义 SNP（CELSR1 的 rs4044210）与缺血性中风的关系。CELSR1 的 rs6007897（A-->G，Thr2268Ala）和 rs4044210（A-->G，Ile2107Val）以及 LLGL2 的 rs1671021（T-->C，Phe479Leu）均与受试者 B 中的缺血性中风显著相关。CELSR1 的 rs6007897 和 rs4044210 多态性也与受试者 C 中的缺血性中风显著相关。
尽管尚未确定所鉴定 SNP 的功能相关性，但 CELSR1 是日本人缺血性中风的易感基因。
