Using the MDR method followed by logistic regression analysis, we showed that the ACE I/D and β-FG T148C polymorphisms were significant synergistic contributors to IS and that the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk for both overall stroke as well as the LAA and SAO subtypes. The gene discussed is ACE; the disease is stroke disorder.