【摘要】 目的研究高血压患者血管紧张素转换酶2(ACE2)基因rs2285666和rs2106809位点多态性与服用苯那普利后长期降压效果的关系,探讨ACE2基因与血管紧张素Ⅱ的1型受体(AGTR1)、血管紧张素原(AGT)基因位点之间的交互作用。方法在上海市南市区,选择苯那普利上市后的3年监测研究中单纯服用苯那普利的全部≥35岁高血压患者,共1 447例,分析ACE2基因rs2285666和rs2106809位点多态性与服药后血压变化指标的关联,并应用广义多因子降维法(GMDR)分析ACE2、AGTR1、AGT基因13个位点间的交互作用。结果 1447例高血压患者中,基线血压达标者181例,占12.5%,基线血压未达标者1 266例,占87.5%;成功鉴定rs2285666基因型者1 230例,其中男性746例,女性484例;成功鉴定rs2106809基因型者1 142例,其中男性668例,女性474例;调整年龄、基线血压指标、首诊药物剂量和尿蛋白水平后,基线血压达标者中,rs2285666位点与男性脉压差变化值有关联(β=0.24,P=0.02),rs2106809位点与男性收缩压差值有关联(β=0.23,P=0.04);基线血压未达标者中,rs2106809位点与女性收缩压差值有关联(β=-0.06,P=0.04);交互作用分析结果表明,男性收缩压变化值、女性收缩压差值和女性舒张压差值存在多位点参与的交互作用模型。结论 ACE2基因rs2285666和rs2106809位点与苯那普利的长期降压效果相关,且在降压过程中ACE2、AGTR1、AGT基因间存在交互作用。更多还原

【Abstract】 Objective To identify the association of the polymorphisms of rs2285666 and rs2106809 in angiotensin-converting 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,AGTR1 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.Conclusionrs2285666 and rs2106809 is associated with the long-term anti-hypertensive effects of benazepril and the interactions exist among genes of ACE2,AGTR1 and AGT.更多还原