Abstract: Objective To identify the association of the polymorphisms of rs2285666 and rs2106809 in angiotensinconverting enzyme 2(ACE2)gene and the anti-hypertensive effects of benazepril,and to explore its interaction with angiotensinⅡtype 1 receptor(AGTR1)gene and angiotensinogen(AGT)gene.Methods Association of the polymorphisms of rs2285666,rs2106809 and the change of blood pressure were identified based on 1 447 hypertensive patients who had been taking only benazepril in a 3-year benazepril postmarket surveillance trial and the interaction of the 13 single-nucleotide polymorphisms(SNPs)from ACE2 gene,AG TR1 gene and AGT gene was explored by the method of generalized multifactor dimensionality reduction(GMDR).Results There were 181(12.5%)patients whose blood pressure were normal and 1 266(87.5%)patients whose blood pressure were abnormal at the beginning of the study.Totally 1 230 patients were successfully indentrfied with the genotype of rs2285666 and 1 142 with rs2106809.Among the male patients whose blood pressure were normal before the study,there were associations between the polymorphism of rs2285666 and the reduction of pulse pressure(β=0.24,P=0.02)as well as rs2106809 and the reduction of systolic blood pressure(β=0.23,P=0.04). Among the female patients whose blood pressure were abnormal before the study,there were associations between the polymorphism of rs210680 and the reduction of systolic blood pressure(β=-0.06,P=0.04).The interaction was found in the systolic blood pressure reduction in both male and female,and that in diastolic pressure reduction in the female.Conclusion rs2285666 and rs2106809 is associated with the long-term anti-hypertensive effects of benazepril and the interactions exist among genes of ACE2,AGTR1 and AGT.