A nonsynonymous SNP in PRKCH (protein kinase C η) increases the risk of cerebral infarction

Michiaki Kubo, Jun Hata, Toshiharu Ninomiya, Koichi Matsuda, Koji Yonemoto, Toshiaki Nakano, Tomonaga Matsushita, Keiko Yamazaki, Yozo Ohnishi, Susumu Saito, Takanari Kitazono, Setsuro Ibayashi, Katsuo Sueishi, Mitsuo Iida, Yusuke Nakamura, Yutaka Kiyohara

研究成果: Article

158 引用 (Scopus)

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Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 × 10-7, crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCη was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction.

元の言語English
ページ(範囲)212-217
ページ数6
ジャーナルNature Genetics
39
発行部数2
DOI
出版物ステータスPublished - 01-02-2007

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All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

Kubo, M., Hata, J., Ninomiya, T., Matsuda, K., Yonemoto, K., Nakano, T., Matsushita, T., Yamazaki, K., Ohnishi, Y., Saito, S., Kitazono, T., Ibayashi, S., Sueishi, K., Iida, M., Nakamura, Y., & Kiyohara, Y. (2007). A nonsynonymous SNP in PRKCH (protein kinase C η) increases the risk of cerebral infarction. Nature Genetics, 39(2), 212-217. https://doi.org/10.1038/ng1945