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
N1 - Funding Information:
We thank the residents of Hisayama and the patients with cerebral infarction for their participation; T. Omae and the staff of the Division of Health and Welfare of Hisayama for their cooperation and many members of the Hisayama study for assistance. For collecting clinical samples, we thank T. Ago, H. Ooboshi, M. Kamouchi, H. Sugimori, J. Kuroda, Y. Kumai, N. Hagiwara and S. Yoshimura (Kyushu University Hospital); K. Tamaki and Y. Wakugawa (Hakujyuji Hospital); K. Fujii (Fukuoka Red Cross Hospital); Y. Okada and K. Toyoda (National Hospital Organization, Kyushu Medical Center); T. Nagao (Imazu Red Cross Hospital); H. Nakane (National Hospital Organization, Fukuoka Higashi Medical Center) and Y. Yamashita and K. Kusuda (Seiai Rehabilitation Hospital). We thank K. Chida (Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo) for technical advice. This study was supported in part by a Special Coordination Fund for Promoting Science and a Fund for Technology and Innovative Development Project in Life Sciences from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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.
UR - http://www.scopus.com/inward/record.url?scp=33846587067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846587067&partnerID=8YFLogxK
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 -