血管紧张素转换酶基因多态性与血管紧张素转换酶抑制剂疗效的相关性

目的　研究原发性高血压 (EH)患者的血管紧张素转换酶 (ACE)基因多态性与血管紧张素转换酶抑制剂 (ACEI)疗效的相关性。方法　 ( 1)用ACEI对 5 17例EH患者进行为期 6周的降压治疗 ,所用药物为咪达普利或苯那普利。 ( 2 )用聚合酶链反应 (PCR)方法检测患者的ACE基因多态性 ,ACE基因有 3种表现型 :II型、DD型和DI型。 ( 3 )治疗前后及治疗过程中对患者的收缩压、舒张压和心率进行监测。结果　 ( 1)在总共 5 17例患者中 ,ACE基因型为DD者有 13 2人( 2 5 5 % ) ,II者有 13 0人 ( 2 5 2 % ) ,ID者有 2 5 5人 ( 4 9 3 % )。 ( 2 )不同基因型组间的性别、年龄、体重指数及心率等的差异无统计学意义。 ( 3 )在这三组患者中 ,治疗前后收缩压的降幅分别为 ( -14 5± 12 7)mmHg ,( -14 3± 13 1)mmHgand( -14 0± 12 2 )mmHg (P =0 94) ,舒张压的降幅分别为 ( -8 7± 7 4)mmHg ,( -8 7± 7 7)mmHgand ( -8 5± 6 7)mmHg (P =0 96)。结论　本研究没有发现EH患者的ACE基因多态性与ACEI的降压疗效相关 ,据此 ,不能根据EH患者的ACE基因型来指导ACEI的降压治疗     

血管紧张素转换酶基因多态性与血管紧张素转换酶抑制剂疗效的相关性

目的研究原发性高血压(EH)患者的血管紧张素转换酶(ACE)基因多态性与血管紧张素转换酶抑制剂(ACEI)疗效的相关性.方法 (1)用ACEI对517例EH患者进行为期6周的降压治疗,所用药物为咪达普利或苯那普利.(2)用聚合酶链反应(PCR)方法检测患者的ACE基因多态性,ACE基因有3种表现型Ⅱ型、DD型和DI型.(3)治疗前后及治疗过程中对患者的收缩压、舒张压和心率进行监测.结果 (1)在总共517例患者中,ACE基因型为DD者有132人(25.5%),Ⅱ者有130人(25.2%),ID者有255人(49.3%).(2)不同基因型组间的性别、年龄、体重指数及心率等的差异无统计学意义.(3)在这三组患者中,治疗前后收缩压的降幅分别为(-14.5±12.7)mmHg,(-14.3±13.1)mmHgand(-14.0±12.2)mmHg(P=0.94),舒张压的降幅分别为(-8.7±7.4)mmHg,(-8.7±7.7)mmHg and(-8.5±6.7)mmHg(P=0.96).结论本研究没有发现EH患者的ACE基因多态性与ACEI的降压疗效相关,据此,不能根据EH患者的ACE基因型来指导ACEI的降压治疗.     

泌尿系统疾病

20041135肾素一血管紧张素系统基因多态性对血管紧张素转换酶抑制剂治疗慢性肾功能不全疗效的影响/陈强一刀肾脏病与透析肾移植杂志一2003,12 (4).一301~306 治疗42例患者中血管紧张素转换酶(ACE)基因的11、Dl及DD基因型分别为1搜例、20例、8例,拍-管紧张素原(AGT)基因的姗、MT及TT基因型分别为5例、22例、15例。均予苯那普利10呢,侮日晨服一次。治疗12个月。结果:治疗ACE基因DD、叮型组Ccr下降速度较H型组略快,DD、DI型组尿蛋白下降幅度显著高于H型组(48.93%、32.56%和9.09%,尸<0.05);AGT基因TT、MT型组Ccr下降速度较翩型组…     

肾素-血管紧张素系统双基因多态性与老年人冠心病慢性心力衰竭的关系

目的:探讨中国南方部分汉族人群的老年冠心病患者中,肾素-血管紧张素系统中的关键成分即血管紧张素转换酶(ACE)及血管紧张素原(AGT)双基因多态性与慢性心力衰竭(心衰)发病的关系.方法:应用聚合酶链反应及限制性片断长度多态性技术,对396例老年冠心病患者的ACE基因插入/缺失(I/D)及AGT基因M235T多态性进行检测.将其中196例合并慢性心衰患者作为病例组,其余200例心功能正常者作为对照组.结果:①病例组DD基因型频率及D等位基因频率均高于对照组;②病例组TT基因型频率及T等位基因频率均高于对照组;③联合分析ACE与AGT基因多态性显示,两组中同时具有DD型ACE基因及TT型AGT基因的频率分别为28.6%及15.0%,前者明显高于后者.结论:DD型ACE基因及TT型AGT基因可能是中国南方部分汉族老年冠心病慢性心衰患者发病的遗传危险因素,ACE和AGT基因在慢性心衰的发生中具有协同作用.     

肾素-血管紧张素系统基因多态性对血管紧张素Ⅱ受体阻断剂降低尿蛋白疗效的影响

目的 :探讨血管紧张素转换酶 (ACE)基因插入 /缺失 (I/D)多态性、血管紧张素Ⅱ 1型受体 (AT1R)基因A116 6 /C多态性和血管紧张素原 (AGT)基因M2 35T多态性是否影响血管紧张素Ⅱ 1型受体阻断剂 (ARB)治疗IgA肾病 (IgAN)患者尿蛋白的疗效。　 方法 :6 4例原发性IgAN患者 ,符合以下条件 :尿蛋白 1～ 3 5g/d ,尿RBC <5 0 0万 /ml,SCr<133μmol/L ,血清白蛋白 >30g/L ;肾活检示肾小球系膜增生性病变或局灶节段性肾小球硬化 ,无新月体及袢坏死 ,小管间质病变轻。治疗方法 :口服缬沙坦 80mg/d 8周。PCR法检测ACE基因I/D多态性、AT1R基因A116 6 /C多态性和AGT基因M2 35T多态性。比较不同基因型患者治疗前后尿蛋白、血压及肾功能变化。　结果 :缬沙坦治疗 8周后 ,患者血压由 (119± 8 10 ) / (78 7± 8 71)mmHg降至 (113± 13 5 ) / (73 0± 10 7)mmHg ,尿蛋白由 (2 0 8± 0 72 )g/d降至 (1 5 8± 0 70 )g/d ,血清白蛋白相应上升 ,但血肌酐及肌酐清除率无明显变化。本试验未观察到AT1R基因型为CC型者。AT1R基因AA型、AC型患者尿蛋白较治疗前分别下降了 (2 4 5± 2 0 1) %,(2 8 5±2 0 0 ) %;ACE基因II型、DI型、DD型患者尿蛋白分别下降了 (2 7 5± 18 4 ) %,(2 3 8± 2 2 6 ) %,(2 2 4± 12 6 ) %;AGT基     

血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

目的　探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂 (ACEI )后发生咳嗽的机制。方法　应用聚合酶链反应 (PCR) ,检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶 (ACE)基因多态性 ,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性。结果　ACEI所致咳嗽组ACE基因Ⅱ型的频率为4 0 % ,显著高于无咳嗽组 (2 0 % ,P <0 0 5 ) ,Ⅰ等位基因频率为 6 0 % ,显著高于无咳嗽组 (4 1% ,P <0 0 1)。两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低。咳嗽组血清ACE水平显著低于无咳嗽组 (P <0 0 0 1) ,血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为 81%和 78%。结论　老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关。     

中国苗族人群血管紧张素原和血管紧张素转化酶基因多态性与冠心病的关系

目的 研究血管紧张素原(ACT)基因M235T分子变异和血管紧张素转化酶(ACE)基因I/D多态性与冠状动脉粥样硬化的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)技术检测冠心病(CHD)组151例和正常对照组127例AGT基因多态性,采用聚合酶链反应技术检测CHD组151例和正常对照组127例ACE基因I/D多态性.结果 CHD组AGT-TT基因型频率为76.26%,显著高于对照组44.10%(P<0.01).ACE-DD基因型频率为35.10%,显著高于对照组14.96%(P<0.01).结论 在中国苗族人群中,AGT基因TT基因型和AGE基因DD基因型是CHD发病既相互独立又具有协同作用的危险因子.     

连锁分析血管紧张素转换酶基因插入/缺失多态性和血管紧张素原 M235T基因多态性与肥厚型心肌病的关系

目的 连锁分析中国人群血管紧张素转换酶（ACE）基因插入／缺失多态性及血管紧张素原（AGT）M235T基因多态性与肥厚型心肌病（HCM）发病的关系。方法 对63例HCM患分别用PCR法检测ACE基因插入／缺失和AGT M235T基因多态性。结果 HCM患中ACE DD＋AGT TT基因型的比数比高于单基因型,其心脏事件发生率高于其他基因型组合和AGT TT型。结论 同时具有ACE DD＋AGT TT基因型,较单基因型发生HCM的风险率显增高;同时具有ACE DD＋AGT TT基因型的HCM患发生心脏事件的危险更大。     

肾素-血管紧张素系统基因多态性与冠心病合并慢性心力衰竭严重程度的关系

目的检测部分中国南方汉族人群冠心病合并慢性心力衰竭患者的ACE及AGT基因多态性分布情况,以探讨肾素-血管紧张素系统（1／AS）基因多态性对冠心病合并慢性心力衰竭严重程度的影响。方法应用聚合酶链反应及限制性片断长度多态性技术,对210例冠心病合并慢性心力衰竭患者的ACE基因插入／缺失（I/D）及AGT基因M235T多态性进行检测,采用彩色多普勒检测患者的左室舒张末内径（LVDD）及左室射血分数（LVEF）。结果不同ACE基因型患者其LVDD及LVEF均存在差异,LVDD（DD）〉LVDD（ID）〉LVDD（II）（P〈0．05）,LVEF（DD）〈IXEF（ID）〈LVEF（II）（P〈0．05）,不同AGT基因型亚组间LVDD及LVEF差别均无统计学意义（P〉0．05）。结论ACE基因I／D多态性与中国南方部分汉族人群冠心病合并慢性心力衰竭的严重程度相关,DD型ACE基因的冠心病患者发生心力衰竭后病情较其他基因型者更加严重。AGT基因M235T多态性似与冠心病合并慢性心力衰竭的严重程度无关。     

血管紧张素转换酶和血管紧张素原基因多态与心肌梗死相关性的研究

目的　探讨血管紧张素转换酶 (ACE)和血管紧张素原 (AGT)基因多态与中国北方人群中心肌梗死 (MI)发病的相关性。方法　采用聚合酶链反应 (PCR)和酶切方法对 90例正常对照者和 6 5例MI患者的ACE插入 /缺失(I/D)多态 ,AGT的M2 35T多态进行检测。结果　MI患者中ACE基因的DD基因型频率 0 431明显高于对照组0 15 6 (P <0 0 1) ,D等位基因频率 0 5 91高于对照组 0 333(P <0 0 1) ,MI患者中AGT基因的TT基因型频率0 6 92高于对照组 0 5 6 7(P <0 0 5 )。结论　DD基因型和TT基因型与中国北方人群心肌梗死相关 ,提示它们是心肌梗死的危险因子。     

ACE2和ACE在自发性高血压大鼠心肌中的变化

目的:观察自发性高血压大鼠(SHR)心肌的血管紧张素转化酶(ACE)和ACE2的表达,以探讨ACE2和ACE在高血压发生发展中的变化。方法:取15只SHR,处死,分离左心室,行RT-PCR、Western blot蛋白质免疫印迹和免疫组织化学检测ACE及ACE2表达;同步取10只WKY大鼠作为正常血压对照组。结果:SHR组心肌ACE的mRNA和蛋白质表达都显著高于WKY组[(1.68±0.34)∶(0.33±0.12),P<0.05;(1.21±0.14)∶(0.71±0.11),P<0.05],而ACE2的mRNA和蛋白质表达皆明显低于WKY组[(0.50±0.15)∶(1.16±0.24),P<0.05;(0.71±0.24)∶(1.22±0.14),P<0.05)]。免疫组织化学染色显示,SHR组ACE的阳性率明显高于WKY组(87%∶50%,P<0.05),而ACE2的阳性率明显低于WKY组(27%∶70%,P<0.05)。结论:SHR心肌ACE明显升高,ACE2显著降低;SHR高血压发生发展过程中存在着ACE和ACE2表达的失衡。     

The Level of Angiotensin-Converting Enzyme as Indicator of 2-Year Prognosis in Untreated Pulmonary Sarcoidosis without Erythema Nodosum

ABSTRACT. In order to evaluate the prognostic significance of elevated serum angiotensin-converting enzyme (SACE) in pulmonary sarcoidosis, the 2-year prognosis was studied in 33 untreated patients without erythema nodosum. Elevated SACE was found in 19 patients among whom total regression or improvement was noted in 42%, against 86% in 14 patients with normal SACE in serial measurements. The groups with and without elevated enzyme levels were not different with respect to sex, age, pulmonary changes, or extrathoracic manifestations. Thus, the finding of elevated SACE in this category of sarcoidosis patients may have some prognostic significance, pointing toward a greater risk of a chronic course.     

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6–56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15–53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14–54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at –20°C for a subsequent test. In HS, fecal ACE activity was 21.03±16.17 nmol/min/100 g (mean ±sd). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 ± 88.94) than in HS and CD on GFD (36.65±23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.     

血管紧张素转换酶基因多态性与卒中

血管紧张素转换酶(ACE)基因是卒中遗传易感性研究的主要候选摹因之一,然而其与卒中的关联性还存在争议.ACE基因多态性与卒中的关系也还不能确定.ACE基因进化树上特定分支可能将取代插入/缺失多态位点,作为卒中的危险标记进行关联性研究.     

Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction

Background: Treatment with an angiotensin-con verting enzyme (ACE) inhibitor in patients with myocardial infarction has been shown to modify endogenous fibrinolysis. Hypothesis: We investigated the effects of the ACE inhibitor imidapril on endogenous fibrinolysis in association with the serum ACE activity. Methods: In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated myocardial infarction, 15 patients received imidapril (5 mg daily) (imidapril group) and another 15 received placebo therapy (placebo group) for 4 weeks. Blood sampling was performed before the start of administration and on Days 3, 7, and 28 after the start of administration. Serum ACE activity and plasma fibrinolytic variables [plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor type 1 (PAI-1) antigen level, and tissue type plasminogen activator (TPA) antigen level] were measured. Results: There was no difference between the imidapril and placebo groups in serum ACE activity or plasma fibrinolytic variables before administration. Serum ACE activity decreased significantly on Days 3, 7, and 28 in the imidapril group. The decrease of PAI activity and PAI-1 antigen levels was significantly less on Days 7 and 28, but not on Day 3. The TPA antigen level in the imidapril group was unchanged. None of the parameters in the placebo group was changed. Conclusion: The ACE inhibitor imidapril modified fibrinolysis, but the effects occurred after the inhibition of serum ACE activity.     

Direct radioimmunoassay of angiotensin-converting enzyme in sera from patients with pulmonary diseases

The concentration of angiotensin-converting enzyme (ACE) was measured in the sera of 47 normal subjects and 108 patients with various pulmonary diseases by radioimmunoassay (RIA) using antiserum to human kidney ACE and homogeneous human kidney ACE as a tracer. The immunologic identity of ACE in the sera from a normal subject and a patient with active sarcoidosis was demonstrated by parallel logit-log transformation of displacement curves in the RIA. The activity and the enzyme concentration in normal and clinical samples correlated well (r=0.78,P<0.001). The mean concentration of ACE in normal serum was 320.9±105.2 ng/ml (mean ±1 SD, n=47). Serum ACE concentration in patients with active sarcoidosis (823.4±209.7, n=13) and in patients with silicosis (569.5±183.8, n=21) was significantly higher than in normals, and the ACE activity in the serum of both groups increased parallel to the concentration. In contrast, patients with active pulmonary tuberculosis (508.5±159.4, n=11) and with lung cancer (481.1±169.5, n=12) had significantly higher serum ACE concentrations (P<0.005) although the serum ACE activity did not increase. The specific activity of both groups (40.4±7.0 and 39.6±7.1 μmol/min/mg, respectively) was lower than that of normal subjects (50.0±12.8). A low ACE activity and a normal ACE concentration in patients with diffuse panbronchiolitis (n=8) and chronic bronchitis (n=6) resulted in a significantly low specific activity (37.4±13.0 and 36.2±7.3, respectively).     

Association between Angiotensin-Converting Enzyme I/D Polymorphism and Asthma Risk: A Meta-Analysis Involving 11,897 Subjects

Background. Genetic susceptibility to asthma has been a research focus in the scientific community. Several studies have been conducted in recent years to evaluate the risk of asthma and insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE). However, the results remain conflicting rather than conclusive. Methods. We carried out a search in Medline, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association. Results. Our meta-analysis on 11,897 subjects from all available studies showed that the DD genotype was associated with increased asthma risk than those with the II (OR = 1.59, 95% CI = 1.20–2.12) or ID/II (OR = 1.62, 95% CI = 1.24–2.10) genotype. Stratified analyses by ethnicity (Europeans and Asians) and age (adults and children) obtained statistically similar results in the two genetic models. In the subgroup analysis by source of controls, the DD genotype was associated with a significantly elevated risk of asthma among population-based controls (DD vs. II: OR = 2.27, 95% CI = 1.45–3.56) but not hospital-based controls (DD vs. II: OR = 1.18, 95% CI = 0.93–1.49). Conclusions. This meta-analysis provides strong evidence that the I/D polymorphism of ACE is associated with asthma risk. Additional well-designed large studies were required for the validation of our results, especially in African populations.     

Variants of renin-angiotensin system genes and echocardiographic left ventricular mass

Aims Variants of renin–angiotensin system genes are shown tobe associated with cardiovascular pathology. The associationbetween renin–angiotensin system genes and left ventricularmass was investigated in a population-based case-control study. Methods and Results The association between echocardiographic left ventricular massand both insertion/deletion polymorphism of the angiotensin-convertingenzyme gene and the methionine|adthreonine variant at position235 of the angiotensinogen gene was studied in a random cohortof 430 hypertensive and 426 control subjects. No differencesin the adjusted left ventricular mass values between the differentgenotypes were seen among either the hypertensive or the controlsubjects, whether men or women, or in the subgroups of normotensiveor physically active subjects. Gene variation had no statisticallysignificant synergistic effect on left ventricular mass values.In control women, the deletion allele of the angiotensin-convertingenzyme gene was associated with an increased risk of left ventricularhypertrophy. However, this finding was based on a small numberof women with left ventricular hypertrophy and should be interpretedwith caution. Conclusion Variations in renin–angiotensin system genes had no majoreffect on left ventricular mass in this middle-aged population-basedcohort of hypertensives and control subjects.     

HOPE for patients with Type 2 diabetes: an application of the findings of the MICRO-HOPE substudy in a British hospital diabetes clinic.

AIMS: The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service. METHODS: Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy. RESULTS: Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively. CONCLUSIONS: Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed.