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

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Abstract

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.

Original languageEnglish
Pages (from-to)212-217
Number of pages6
JournalNature Genetics
Volume39
Issue number2
DOIs
Publication statusPublished - 02-2007

All Science Journal Classification (ASJC) codes

  • Genetics

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    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