title: A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction.
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 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.
authors.affiliation: Department of Environmental Medicine, Kyushu University, Fukuoka 812-8582, Japan. mkubo@ims.u-tokyo.ac.jp
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Jun
authors.initials: J
authors.lastname: Hata
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Koji
authors.initials: K
authors.lastname: Yonemoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Matsushita
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yozo
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Susumu
authors.initials: S
authors.lastname: Saito
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.forename: Setsuro
authors.initials: S
authors.lastname: Ibayashi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Iida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
mesh_terms: 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*
chemical_list: C081975:protein kinase C eta; D011493:Protein Kinase C