Recently, a large-scale genetic epidemiological study has shown significant association of single nucleotide polymorphisms (SNPs) in the protein kinase C eta (PRKCH) gene with cerebral infarction, particularly, with lacunar infarction. To extend the findings, we tested association of two SNPs previously reported--rs3783799 and rs2230500--in PRKCH with silent lacunar infarction (SLI), which has drawn substantial attention in the aging societies. Disease association was tested in the case-control study design. Subjects with and without SLI were recruited from people who underwent a health-screening examination including brain MRI. Two SNPs were genotyped and proven to be in complete linkage disequilibrium (D'=1.00, r(2)=1.00) and thus showed comparable results of disease association, which were reproduced in two panels collected independently. In the entire population involving 295 cases and 497 controls, two SNPs remained to be significantly associated with SLI under a dominant model even after adjustment for confounding factors such as hypertension (e.g., genetic effects of rs2230500, P=0.0026 for AA+AG vs. GG, adjusted odds ratio=1.27; 95% CI, 1.09-1.48). As the two SNPs appear to be common only in Asian people, further replication study is warranted in the other Asian populations as well as the Japanese.