The present study aimed to investigate the interaction between the Ser447Term polymorphism in the lipoprotein lipase (LPL) gene and some common risk factors for stroke. A total of 704 unrelated patients with ischemic stroke were recruited for genetic analysis; they were all of Han Chinese origin. These patients were classified into subgroups based on their exposure to stroke-related risk factors, including type 2 diabetes, hypertension, smoking, and hyperlipidemia. The Ser447Term polymorphism was genotyped by PCR-based restriction fragment length polymorphism analysis. The chi-square (? 2) test showed that the frequency of Ser447Term G allele was significantly higher in stroke patients with a history of diabetes than in those without a history of diabetes (? 2 = 7.25, P = 0.007, OR = 1.78, 95%CI 1.18-2.68). Allelic association was not observed in patients exposed to the other three stroke-related risk factors. The combined effect of the LPL gene polymorphisms and diabetes may contribute to the development of a subgroup of ischemic stroke. ? 2010 Springer Science+Business Media, LLC.