A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction.
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.
Kubo
Michiaki
M
Department of Environmental Medicine, Kyushu University, Fukuoka 812-8582, Japan. mkubo@ims.u-tokyo.ac.jp
Hata
Jun
J
Ninomiya
Toshiharu
T
Matsuda
Koichi
K
Yonemoto
Koji
K
Nakano
Toshiaki
T
Matsushita
Tomonaga
T
Yamazaki
Keiko
K
Ohnishi
Yozo
Y
Saito
Susumu
S
Kitazono
Takanari
T
Ibayashi
Setsuro
S
Sueishi
Katsuo
K
Iida
Mitsuo
M
Nakamura
Yusuke
Y
Kiyohara
Yutaka
Y
D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics; D005500:Follow-Up Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011493:Protein Kinase C / Q000235:genetics*
C081975:protein kinase C eta; D011493:Protein Kinase C