【作者】 李传方；

【导师】 高东升； 杨志寅；

【作者基本信息】 山东大学 ， 内科学， 2010， 硕士

【摘要】 目的探讨血管紧张素Ⅱ2型受体基因多态性对钙拮抗剂降压疗效的影响,对钙拮抗剂与AT2受体基因多态性的关系做初步探索,为高血压的药物个体化治疗、疗效预测提供一定的理论依据。对象和方法本研究的病例源于山东省济宁医学院附属医院心内科病房、门诊、健康查体中心,300例新发原发性轻、中度高血压患者,排除继发性高血压、急性心、脑血管病,以及心、肝、肾功能不全、未控制的糖尿病患者。实验前停用其他降压药物2周,测量基础血压后,第2天开始服用硝苯地平控释片(钙离子拮抗剂,商品名：拜新同)30mg／d,连续服用8周。测量患者诊室坐位右上臂血压,均采用水银袖带血压计,于开始服药后第2周、4周、6周、8周时上午测量,每次测量3次,取平均值。同时对患者进行体格检查及留取患者静脉血5mL,2%EDTA抗凝,测量生化指标和提取DNA。用聚合酶链反应(PCR)结合高分辨率熔解曲线(HRM)、基因测序方法检测患者的AT2受体基因多态性。观察AT2受体不同基因型与钙离子拮抗剂降压疗效的关系。结果共300例患者入选了该实验,最终有229例患者完成了8周的实验,并成功的进行了全血基因组DNA的提取和多态性分析。女性患者116例,AA、AG及GG基因型分别为31例(26.7%)、62例(53.5%)和23例(19.8%),A和G等位基因频率分别为：53.4%和46.6%。治疗8周后基因型AA患者SBP及DBP降压幅度分别为：19.84±9.89和12.71±7.70,AG型患者降幅分别为：21.00±12.42和14.03±9.49,GG型患者降幅分别为：20.04±12.05mmHg和13.52±3.85mmHg；降压有效率分别为：71.0%、74.2%、76.0%；三组比较差异无统计学意义(p>0.05)。男性113例,AA型61例(54.0%),GG型52例(46.0%),AA型与GG型SBP、DBP降压幅度分别为：20.20±9.25mmHg和14.69±6.61mmHg,21.75±12.07mmHg和13.75±7.22mmHg；降压有效率分别为：73.8%和75.0%。在这两组患者中,降压幅度、治疗有效率的差异无统计学意义(P>0.05)。结论1、AT2受体基因1675A／G多态性对钙拮抗剂(硝苯地平控释片)降压幅度及疗效无明显影响。2、AT2受体基因1675A／G女性等位基因频率：A为53.4%、G为46.6%,男性等位基因频率：A为54.0%,G为46.0%,无论男、女等位基因频率与国内外同类研究结果基本一致。3、长效钙拮抗剂(硝苯地平控释片)单药治疗轻、中度高血压效果确切,可作为其一线降压药物。更多还原

【Abstract】 Objective To explore the effect of angiotensinⅡtype 2 receptor gene polymorphism on blood pressure response to CCB and to preliminarily discuss the relationship between CCB and AT2 receptor gene polymorphism so as to provide some scientific evidence for individual therapy and healing prediction.Subjects and Methods In the research,300 new essential hypertension patients who were light and medium level were selected randomly from medicine-department clinic service,department of cordis and center of examination.Subjects with a history of cardiac or hepatic,diabetes mellitus were excluded,no symptoms of heart failure,stroke and lower-linber arterial disease. All patients have received Nifedipine Controlled Release Tablets (30mg/qd) for 8 weeks and no antihypertensive therapy for preceding two weeks,all patients’blood pressure were measured 3 times at 2,4,6,8week in the clinic service and mean value were registered as BP value. Took down their individual information (including name, sex, age, region, et al).Venous blood (5mL) were collected for measuring biochemical indicator and excluding DNA. The blood samples from the patients were collect to determine their AT2 receptor gene polymorphism by PCR combined with HRM,sequencing. The relationship among the genotypes of AT2 receptor to the therapeutic efficacy of Nifedipine was explored.Results A total of 300 qualfied patients were enro11ed in the trial.229 patients completed the final 8-week trial. A whole blood genomic DNA extraction successfully conducted and and their data were used for the polymorphism analysis. Women with 116 cases,AA,AG and GG genotypes were 31 cases (26.7%),62 cases (53.5%) and 23 cases (19.8%), A and G allele frequencies were as follows:53.4% and 46.6%. After 8 weeks, in patients with AA genotype SBP and DBP, respectively decreasing amplitude:19.84±9.89 and 12.71±7.70, AG genotype patients, respectively drop amplitude:21.00±12.42 and 14.03±9.49, GG genotype patients, respectively drop amplitude:20.04±12.05mmHg and 13.52±3.85mmHg; Antihypertensive efficiency for three genotypes (AA、AG、GG) are as follows: 71.0%,74.2%,76.0%; three genotypes difference was not statistically significant (p> 0.05). Male 113 cases, AA genotype was 61 cases (54.0%), GG genotype was 52 cases (46.0%), AA genotype and GG genotype SBP, DBP drop range, respectively: 20.20±9.25mmHg and 14.69±6.61mmHg,21.75±12.07mmHg andl3.75±7.22mmHg;Antihypertensive efficiency for two genotypes(AA,GG)are as follows:73.8% and 75.0%. In both sets of patients, blood pressure reduction and the therapeutic efficacy of the difference were not statistically significant (P> 0.05).Conclusion 1.The 1675A/G polymorphism of AT2 receptor gene was shown to no influence the response to CCB (Nifedipine Controlled Release Tablets).2.AT2 receptor gene 1675A/G allele frequencies of women:A of 53.4%, G 46.6%, male allele frequencies:A of 54.0%, G 46.0%, both male and female allele frequencies at home and abroad Similar findings are basically consistent.3. Confirmed that Nifedipine Controlled Release Tablets in patients with mild to moderate hypertension has antihypertensive effect of the exact.更多还原