[Genome-wide association study for ischemic stroke based on the Hisayama study].

Jun Hata, Michiaki Kubo, Yutaka Kiyohara

研究成果: ジャーナルへの寄稿評論記事

11 引用 (Scopus)

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Ischemic stroke is a major cause of death and disability, and occurs owing to a combination of multiple environmental and genetic risk factors. Although twin studies and family-based studies have suggested the existence of genetic risk factors for ischemic stroke, few candidate genes have been discovered. To identify genes for susceptibility to ischemic stroke, we performed a genome-wide association study using 52,608 single nucleotide polymorphism (SNP) markers. After comparison of allele frequencies between 1,112 patients with ischemic stroke and the same number of age- and sex-matched control subjects, who were selected from among the residents of the town of Hisayama, Japan, we identified three novel candidate genes for ischemic stroke: PRKCH (protein kinase C eta (PKCη)), AGTRL1 (apelin receptor), and ARHGEF10 (Rho guanine nucleotide exchange factor 10). In the functional analyses, we found that PKCη was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and that the kinase activity of PKCη was modified by a nonsynonymous SNP in PRKCH (rs2230500). We also clarified that functional SNPs in AGTRL1 (rs9943582) and ARHGEF10 (rs4376531) affected transcriptional activities owing to the different Sp1-binding affinities. In a 14-year follow-up cohort study of Hisayama residents, all of these SNPs were significantly associated with the development of ischemic stroke. Although the mechanisms of these genes in the pathogenesis of ischemic stroke are still to be elucidated, our findings might contribute to a better understanding of ischemic stroke in the future.

元の言語英語
ページ(範囲)47-52
ページ数6
ジャーナルNihon eiseigaku zasshi. Japanese journal of hygiene
66
発行部数1
DOI
出版物ステータス出版済み - 1 2011

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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