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

被引：167

作者：

Kubo, Michiaki ^{[1
]}

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

机构：

[1] Kyushu Univ, Dept Environm Med, Fukuoka 8128582, Japan

[2] Kyushu Univ, Dept Med & Clin Sci, Fukuoka 8128582, Japan

[3] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genet, Tokyo 1088639, Japan

[4] Kyushu Univ, Grad Sch Med Sci, Fukuoka 8128582, Japan

[5] RIKEN, Lab Genotyping, SNP Res Ctr, Inst Phys & Chem Res, Yokohama, Kanagawa 2300045, Japan

来源：

NATURE GENETICS | 2007年 / 39卷 / 02期

关键词：

D O I：

10.1038/ng1945

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cerebral infarction is the most common type of stroke an 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 X 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 PKC eta 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.

引用

页码：212 / 217

页数：6

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