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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。
Objective To investigate the relationship between polymorphism of rs2285666 and rs2106809 of angiotensin converting enzyme 2 (ACE2) gene and long-term antihypertensive effect after benazepril treatment in hypertensive patients and to explore the relationship between ACE2 gene and angiotensin Ⅱ type 1 receptor (AGTR1), angiotensinogen (AGT) gene locus. Methods A total of 1 447 hypertensive patients with benazepril alone were enrolled in the 3-year monitoring study after benazepril marketed in Shanghai’s Nanshi District. A total of 1 447 cases of ACE2 gene rs2285666 and rs2106809 loci were analyzed And the changes of blood pressure after taking medication, and analyzed the interaction of ACE2, AGTR1 and AGT gene 13 loci by using generalized multi-factor dimensionality reduction method (GMDR). Results Of the 1447 hypertensive patients, 181 (12.5%) achieved baseline blood pressure compliance and 1266 (87.5%) failed to meet baseline blood pressure criteria. A total of 1,230 rs2285666 genotypes were successfully identified, including 746 males and 484 females ; 1 142 cases of rs2106809 genotype were successfully identified, including 668 males and 474 females. After adjustment for age, baseline blood pressure, first-aid dose and urinary protein levels, rs2285666 locus was positively correlated with male pulse pressure (Β = 0.24, P = 0.02). The rs2106809 locus was associated with the difference of systolic blood pressure (β = 0.23, P = 0.04). In the non-compliance of baseline blood pressure, rs2106809 was associated with female systolic pressure (Β = -0.06, P = 0.04). The results of the interaction analysis showed that there was a multi-site interaction model between male systolic blood pressure changes, female systolic blood pressure and female diastolic blood pressure. Conclusion The ACE2 gene rs2285666 and rs2106809 sites are related to long-term antihypertensive effect of benazepril and ACE2, AGTR1 and AGT genes are interacted during the antihypertensive process.