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.     

血管紧张素原基因T174M和血管紧张素转换酶基因I/D多态性与急性心肌梗死的相关性

目的探讨中国汉族人群血管紧张素转换酶和血管紧张素原基因型的分布及其与急性心肌梗死的关系。方法应用聚合酶链反应技术,对112例急性心肌梗死患者、128例非冠心病患者血管紧张素转换酶I/D多态性及血管紧张素原T174M多态性进行检测。结果血管紧张素转换酶基因型分布及等位基因频率在病例组及对照组间差异有显著性(P<0.01)。病例组和对照组血管紧张素原基因型及等位基因频率总体分布差异亦有显著性(P<0.05)。联合基因分析显示,急性心肌梗死组血管紧张素转换酶DD基因型 血管紧张素原174MM基因型频率显著高于对照组(P<0.01),具有该联合基因型者发生冠心病的风险比数比(OR=8.467)明显高于单独具有血管紧张素转换酶DD基因型(OR=2.558)或血管紧张素原174MM基因型(OR=6.176)者。结论血管紧张素原T174M基因多态性中M等位基因和血管紧张素转换酶I/D基因多态性基因中的D等位基因是中国汉族人群冠心病发病的危险因素之一。同时具有血管紧张素转换酶DD型及血管紧张素原174MM型发生冠心病的相对风险显著高于单基因血管紧张素转换酶DD型及单基因血管紧张素原174MM型。     

冠心病患者动脉弹性与血管舒张功能受损的关系

目的探讨冠心病患者动脉弹性和内皮与非内皮依赖性血管舒张功能的关系。方法采用高分辨率血管超声法检测30例冠心病患者(冠心病组)与健康体检非冠心病者30例(对照组)肱动脉血流介导的内皮依赖性血管舒张功能及硝酸甘油介导的非内皮依赖性血管舒张功能;动脉弹性功能检测仪测定受试者的大动脉弹性指数(C1)和小动脉弹性指数(C2)。结果冠心病组与对照组的C1差异无显著性意义,但冠心病组的C2明显低于对照组,冠心病组内皮依赖性血管舒张功能与非内皮依赖性血管舒张功能均明显低于对照组;冠心病组C2不仅与内皮依赖性血管舒张功能呈正相关,且同非内皮依赖性血管舒张功能呈正相关。结论冠心病组C2降低,C2降低不仅同血管内皮功能的受损相关,而且也受非内皮因素的影响,提示C2反映总体血管舒张功能受损的程度。     

血管紧张素转换酶基因多态性与冠脉病变严重程度的相关性研究

目的探讨血管紧张素转换酶(ACE)基因I/D多态性与冠心病及冠脉病变严重程度的关系.方法对122例冠心病患者进行冠状动脉造影,判定冠脉病变支数(狭窄程度≥75%)和危险记分.用聚合酶链式反应(PCR)技术检测病例组和80例健康人群ACE基因多态性.结果ACE基因型分布和等位基因频率在病例组和对照组间差异有显著性,病例组DD基因型(38.5%)和D等位基因频率(55%)显著高于对照组(13.7%,41%;P＜0.05).冠脉病变支数和危险记分在ACE基因型间差异无显著性(P＞0.05).结论ACE基因多态性中DD型和D等位基因是冠心病发病的独立危险因素,但与冠脉病变严重程度不相关.     

肾素-血管紧张素系统基因多态性与冠心病的关系

目的探讨肾素-血管紧张素系统三个关键基因血管紧张素转化酶基因插入/缺失多态性、血管紧张素原基因M235T多态性及血管紧张素Ⅱ1型受体基因A1166/C多态性与冠心病的关系。方法应用多聚酶链反应-限制片长多态性方法对110例冠心病患者和80例健康人分别进行单基因和基因连锁分析。结果①冠心病组血管紧张素转化酶基因DD基因型(43.6%)及D等位基因频率(60.5%)明显高于正常对照组(分别为26.3%和44.4%,P<0.05);血管紧张素原基因TT基因型(66.4%)及T等位基因频率(78.6%)亦明显高于正常对照组(分别为42.5%和60.6%,P<0.05);与正常对照组相比,冠心病组血管紧张素Ⅱ1型受体基因的AA、AC基因型频率和A、C等位基因频率差异均无显著性(P>0.05)。②联合分析三个基因多态性罹患冠心病的相对风险,其OR为3.395,高于单基因血管紧张素转化酶DD型(OR为2.175)及血管紧张素原TT型(OR为2.669),低于血管紧张素转化酶DD型 血管紧张素原TT型(OR为6.098)。结论血管紧张素转化酶基因插入/缺失多态性及血管紧张素原基因M235T多态性与冠心病有关,而血管紧张素Ⅱ 1型受体基因A1166/C多态性可能与冠心病无关联。同时具有血管紧张素转化酶DD型及血管紧张素原TT型者发生冠心病的相对风险显著增高。     

血管紧张素转移酶基因插入/缺失多态性与胃癌的相关性

目的 探讨血管紧张素转移酶(ACE)基因插入(I)/缺失(D)多态性与胃癌的相关性.方法 采用聚合酶链反应(PCR)法检测181例胃癌组和198例健康对照组ACE基因L/D多态性.结果 胃癌组与对照组ACEI/D基因型和等位基因分布差异不显著(P＞0.05).根据临床特征进行亚组分析,发现低分化胃癌患者中DD基因型频率明显高于高中分化(P=0.002);有转移的胃癌患者中DD基因型频率明显高于未转移(P=0.012).结论 ACE基因L/D多态性与胃癌的分化程度和转移状态等影响胃癌预后的临床病理特征密切相关.     

冠心病患者血管紧张素转换酶基因多态性及其与血清血管紧张素转换酶水平的关系

为研究冠心病患者血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性分布及其与血清ACE水平的相关性，应用多聚酶链反应方法测定了61例冠心病患者和63例健康人群的ACE基因I／D多态性，并采用微量比色法测定其血清ACE水平。结果发现，冠心病患者ACE基因DD型出现频率显著高于对照组，且DD基因型者具有较高的血清ACE水平。提示ACE基因I／D多态性与血清ACE水平密切相关，DD型ACE基因可能是中国人冠心病发病的独立危险因子。     

血管紧张素转化酶基因多态性与内皮功能的研究

目的 :探讨血管紧张素转化酶 （ACE）基因多态性与冠心病血管内皮功能的关系。方法 :采用多聚酶链反应（PCR）技术对 2 4例心肌梗死、5 6例心绞痛患者、6 5例正常人的 ACE基因型及血浆内皮素 （ET）、内皮源性舒张因子 （EDRF）进行了检测 ,以 ET/ NO作为内皮功能指标。结果 :心肌梗死组 D等位基因频率显著高于正常对照组 ,DD型患者中的 ET/ NO比值较 型明显升高 （P<0 .0 5 ）。结论 :DD型心肌梗死患者内皮功能受损较重。     

血管紧张素转换酶和血管紧张素受体基因多态性与冠心病的关系

目的　探讨深圳地区冠心病 (CAD)与血管紧张素转换酶 (ACE)基因与血管紧张素 的 1型受体 (AT1R)基因多态性的关系。方法　分别采用 PCR及 PCR- Afl II酶切法 ,检测 89例 CAD患者和 14 8例健康对照的 ACE和AT1R基因型。结果　 CAD组与对照组比较 ,ACE DD基因型频率 (2 4 .7%比 8.1% ,P<0 .0 1)及 D型等位基因频率 (4 4 .4 %比 33.4 % ,P<0 .0 5 )均为升高。 CAD组与对照组 AT1R基因型频率分布无显著性差异 (P>0 .0 5 )。携带 AT1R C等位基因的个体患 CAD的风险与其同时携带 ACE DD基因型无关 (P>0 .0 5 )。结论　深圳地区CAD的发生和发展可能与 ACE基因 I/ D多态性有关 ,而与 AT1R基因 A116 6 C多态性无关     

血管紧张素转换酶基因与冠状动脉粥样硬化关系的研究

目的　探讨血管紧张素转换酶 (ACE)基因多态性与冠状动脉粥样硬化的关系。方法　 14 6例冠心病(CAD)患者按ACE基因型分为缺失型纯合子 (DD)、杂合子 (ID)及插入型纯合子 (II) 3组 ;Bogaty标准评价冠状动脉造影结果 ;马尿酸微量比色法测量血清ACE水平。结果　⑴Bogaty各指标评价结果与左室射血分数 (LVEF)及左室舒张末压 (LVEDP)明显相关。⑵DD型CAD患者冠脉病变较ID及II型严重。⑶DD型CAD患者血清ACE水平高于ID及II型。结论　⑴ACE基因多态性与CAD患者冠状动脉病变有关。⑵血清ACE水平可能为二者相关的机制。⑶Bogaty标准能全面准确地反映CAD患者冠状动脉病变特征及左室功能下降程度。     

冠心病患者血管紧张素转换酶基因多态性及其与血清血管紧张素转换酶水平的关系

为研究冠心病患者血管紧张素转换酶（ＡＣＥ），基因插入／缺失（Ｉ／Ｄ）多态性分布及其血清ＡＣＥ水平的相关性，应用多聚酶链反应方法测定了６１例冠心病患者和６３例健康人群的ＡＣＥ水平，结果发现，冠心病患者ＡＣＥ基因ＤＤ型出现频率显著对照组，且ＤＤ基因型者具有较高的血清ＡＣＥ水平，提示，ＡＣＥ基因Ｉ／Ｄ多态性与血清ＡＣＥ水平密切相关，ＤＤ型ＡＣＥ基因可能是中国人冠心病发病的独立危险因子。     

对氧磷酶1基因192位Gln/Arg多态性对冠心病患者内皮功能的影响

目的研究国人血清对氧磷酶1（PON1）基因192位Gln/Arg多态性对冠心病患者血管内皮功能的影响。方法应用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）方法,对石家庄地区汉族151例冠心病患者及91例正常对照者PON1基因192位Gln/Arg多态性进行分析,同时应用超声检测肱动脉内皮功能。结果冠心病组及正常对照组PON1基因均以QR基因型为主,其频率分别为48%和54%。冠心病组RR型基因频率高于对照组（P<0.05）。平衡法计算等位基因的频率,R等位基因在冠心病组明显增高（65%vs39%,P<0.05）。冠心病组PON1各基因型内皮依赖性舒张功能均低于对照组（P<0.05）,以RR基因型最为明显,其次为QR基因性;而两组非内皮依赖性舒张功能差异无显著性。结论PON1基因192位Gln/Arg多态性可能与冠心病患者血管内皮功能异常有关。R等位基因可能为血管内皮功能受损的相对危险因素,且参与冠心病的发病。     

血管紧张素转化酶基因插入/缺失多态性与冠心病发病的关系

目的 :探讨血管紧张素转化酶 (ACE)基因多态性与冠心病 (CHD)发病的关系。方法 :以人基因组DNA为模板 ,应用聚合酶链式反应 (PCR)检测 5 0例CHD组和 5 6例正常对照组ACE基因第 16内含子插入 /缺失 (I/D)多态性 ,并按性别分组计算各组基因型和等位基因频率。结果 :①在CHD组中 ,ACE基因DD基因型和D等位基因频率分别为 36 %和 6 0 % ,正常对照组分别为 16 %和 4 1% ,两者相比差异有统计学意义 (P <0 .0 1)。②男性CHD组DD基因型和D等位基因频率均显著高于对照组 (均P <0 .0 5 )。女性CHD组DD基因型频率显著高于对照组 (P <0 .0 1) ,D等位基因频率与对照组比较差异无统计学意义。结论 :CHD与ACE基因I/D多态性有显著相关性 ,不论男性和女性 ,ACE基因DD基因型均可能是CHD发生发展过程中重要的危险因素之一。     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.     

Improved endothelium dependent vasodilation in endurance athletes and its relation with ACE I/D polymorphism.

BACKGROUND: Aerobic exercise enhances endothelium-dependent vasodilation in healthy individuals. It is thought that exercise increases nitric oxide (NO) production and decreases NO inactivation, leading to an increase in NO bioavailability. Angiotensin II and NO have important roles in maintaining vascular tone. There are polymorphisms of the angiotensin converting enzyme (ACE) gene and the presence of the deletion (D) allele has been associated with higher concentrations of circulating and tissue ACE. In this study, the relationship between endothelial function and ACE gene polymorphisms was investigated in athletes and sedentary subjects. METHODS AND RESULTS: The study group comprised 56 endurance athletes and 46 sedentary subjects who underwent brachial artery ultrasonographic examination. ACE insertion (I) and D allele frequencies were analyzed in all patients. Baseline brachial artery diameter and resting blood flow were similar in athletes and controls (p > 0.05). The flow-mediated dilation (FMD) was 8.48+/-3.65% in athletes and 5.16+/-2.5% in controls (p = 0.0001). FMD was significantly different between ACE genotypes in the athletes (p < 0.0001): it was higher in ACE II (10.5+/-1.6%) subjects than in the DI (8.4+/-2.3%) or DD (7+/-1.2%) subgroups. CONCLUSION: Regular isotonic exercise can improve endothelium-dependent vasodilation especially in those with the ACE II genotype.     

ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.     

Angiotensin-converting enzyme gene polymorphism in Kuwaiti patients with systemic lupus erythematosus

OBJECTIVE: To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in patients with systemic lupus erythematosus (SLE), and to study the correlation between I/D polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement, lupus nephritis and disease severity. METHODS: The frequency of ACE gene I/D polymorphism genotypes was determined in 92 patients with SLE from Kuwait, and compared to that in 100 ethnically matched healthy controls using the polymerase chain reaction. RESULTS: The distribution of ACE I/D polymorphism and allele frequencies in SLE patients was not significantly different from controls. Further analyses of SLE patients showed that there was a significant association between DD genotype and Raynaud's phenomenon (p=0.008, odd ratio=5.4, 95% confidence interval: 1.6-18.6). However, there was no significant association between the ACE genotype and lupus nephritis or disease severity. CONCLUSION: No difference was found between the distribution of the ACE genotype in SLE patients and the general pop-ulation in Kuwait. However, the presence of the DD genotype may confer susceptibility to the development of vascular morbidity.     

ACE基因I/D多态性与冠状动脉支架内再狭窄相关性研究

目的研究冠状动脉内行药物洗脱支架置入术患者,术后支架内再狭窄发生情况与ACE基因I/D多态性的关系。方法所有患者行冠状动脉造影检查,PCR方法测定ACE基因型。根据血管造影结果分为再狭窄组（病变狭窄≥50%）和无再狭窄组（病变狭窄〈50%）。采用SPSS18.0软件比较再狭窄组与无再狭窄组的临床基本特征、冠脉造影资料,以及与ACE基因型的关系。结果此次研究共纳入396名行药物洗脱支架置入术的冠心病患者,支架内再狭窄发生40例,再狭窄率为10.1%。再狭窄组与无再狭窄组的临床基本资料、冠脉造影资料均无显著性差异（P〉0.05）。再狭窄组的ACEDD基因型35.56%、ACEDI基因型16.39%、ACEII基因型3.85%。再狭窄组与ACE基因I/D多态性具有相关性（P〈0.001）。结论冠状动脉内行药物洗脱支架置入术患者术后支架再狭窄发生与ACEDD基因型具有显著相关性。     

Angiotensin-converting enzyme gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients

OBJECTIVE: It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) may be associated with atherosclerosis.The aim of the study was to examine the association between ACE gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients. METHODS AND RESULTS: A total of 152 (97 female, 55 male) type 2 diabetic patients were included into the study. All patients underwent myocardial perfusion scintigraphic examination and forty-five of them with a perfusion defect underwent coronary angiography.Thirty-eight patients with a coronary stenosis of more than 50% on coronary angiography were considered as having coronary heart disease.The I/D polymorphism was determined by polymerase chain reaction.There was no statistically significant difference in genotypic and allelic frequencies of the ACE I/D polymorphism among patients with and without coronary heart disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). CONCLUSIONS: ACE gene polymorphism is not a significant parameter to determine coronary heart disease in Turkish type 2 diabetic patients.