We performed a case-control study of MetS based on the health check-up data of Japanese male employees and found significant associations of five SNPs with MetS, including LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we identified a novel SNP × CP interaction for MetS, which was the interaction between VWF rs7965413 and platelet count. This evidence concerns the gene VWF and metabolic syndrome.