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 - 01-02-2007

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Cerebral Infarction
Protein Kinase C
Single Nucleotide Polymorphism
Lacunar Stroke
Case-Control Studies
Japan
Cohort Studies
Endothelial Cells
Stroke
Macrophages
Odds Ratio
Databases
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Kubo, M., Hata, J., Ninomiya, T., Matsuda, K., Yonemoto, K., Nakano, T., ... 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
Kubo, Michiaki ; Hata, Jun ; Ninomiya, Toshiharu ; Matsuda, Koichi ; Yonemoto, Koji ; Nakano, Toshiaki ; Matsushita, Tomonaga ; Yamazaki, Keiko ; Ohnishi, Yozo ; Saito, Susumu ; Kitazono, Takanari ; Ibayashi, Setsuro ; Sueishi, Katsuo ; Iida, Mitsuo ; Nakamura, Yusuke ; Kiyohara, Yutaka. / A nonsynonymous SNP in PRKCH (protein kinase C η) increases the risk of cerebral infarction. In: Nature Genetics. 2007 ; Vol. 39, No. 2. pp. 212-217.
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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, vol. 39, no. 2, pp. 212-217. https://doi.org/10.1038/ng1945

A nonsynonymous SNP in PRKCH (protein kinase C η) increases the risk of cerebral infarction. / Kubo, Michiaki; Hata, Jun; Ninomiya, Toshiharu; Matsuda, Koichi; Yonemoto, Koji; Nakano, Toshiaki; Matsushita, Tomonaga; Yamazaki, Keiko; Ohnishi, Yozo; Saito, Susumu; Kitazono, Takanari; Ibayashi, Setsuro; Sueishi, Katsuo; Iida, Mitsuo; Nakamura, Yusuke; Kiyohara, Yutaka.

In: Nature Genetics, Vol. 39, No. 2, 01.02.2007, p. 212-217.

Research output: Contribution to journalArticle

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T1 - A nonsynonymous SNP in PRKCH (protein kinase C η) increases the risk of cerebral infarction

AU - Kubo, Michiaki

AU - Hata, Jun

AU - Ninomiya, Toshiharu

AU - Matsuda, Koichi

AU - Yonemoto, Koji

AU - Nakano, Toshiaki

AU - Matsushita, Tomonaga

AU - Yamazaki, Keiko

AU - Ohnishi, Yozo

AU - Saito, Susumu

AU - Kitazono, Takanari

AU - Ibayashi, Setsuro

AU - Sueishi, Katsuo

AU - Iida, Mitsuo

AU - Nakamura, Yusuke

AU - Kiyohara, Yutaka

PY - 2007/2/1

Y1 - 2007/2/1

N2 - 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.

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