TY - JOUR
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
Y1 - 2007/2
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.
AB - 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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U2 - 10.1038/ng1945
DO - 10.1038/ng1945
M3 - Article
C2 - 17206144
AN - SCOPUS:33846587067
VL - 39
SP - 212
EP - 217
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -