Objective To explore the interaction between polymorphisms of rs17222919 which located in the 5-1ipoxygenase-activating protein(ALOX5AP) gene promoter and environmental risk factors in ischemic stroke(IS).Methods We conducted a case-control study involving a total of 622 cases and 631 unrelated healthy controls which were selected from Henan Han populations,and the environment risk factors were recorded.Genotyping aimed at detecting both genetic and environmental factors in relation to IS was performed by TaqMan-polymerase chain reaction technology while interaction indexes (Υ) were calculated to determine interactions and their role models.Results The rs17222919 TG (189/622,30.4％),GG (18/622,2.9％)genotype frequencies and G (225/1244,18.1％)allele frequencies in IS subjects were significantly lower than those in controls (221/631,35.0％ ; 31/631,4.9％ ; 283/1262,22.4％ ; x2 =4.117,P =0.042 ; x2 =4.457,P =0.035 ; x2 =7.294,P =0.007).Negative interactions between TG + GG genotype and hypertension,diabetes or cigarette smoking in the occurrence of IS (Υ =0.943,0.922,0.830) were observed,whose role models were all super-multiplicative models.Conclusions According to our study,ischemic stroke is the result of the interaction of genetic and environmental factors and G allele of rs17222919 may have weakened the role of environmental factors for hypertension,diabetes and cigarette smoking in IS incidence.