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
Department of Environmental Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Nat Genet. 2007 Feb;39(2):212-7. doi: 10.1038/ng1945. Epub 2007 Jan 7.
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 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 PKCeta 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.
脑梗死是最常见的中风类型，常导致长期残疾。为了研究基因对脑梗死的影响，我们使用从JSNP数据库中选取的52608个基于基因的标签单核苷酸多态性（tag SNPs）进行了一项病例对照研究。在此我们报告，蛋白激酶C（PKC）家族成员PRKCH中的一个非同义单核苷酸多态性与两个独立的日本样本中的腔隙性脑梗死显著相关（P = 5.1 x 10^(-7)，粗比值比为1.40）。该单核苷酸多态性可能影响PKC活性。此外，在日本福冈久山进行的一项为期14年的队列研究支持该单核苷酸多态性参与脑梗死的发生发展（P = 0.03，年龄和性别调整后的风险比为2.83）。我们还发现，PKCeta主要在人类动脉粥样硬化病变的血管内皮细胞和泡沫巨噬细胞中表达，并且其表达随着病变类型的进展而增加。我们的结果支持PRKCH在脑梗死发病机制中的作用。
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