血管紧张素转化酶基因多态性与原发性高血压无关

目的 研究血管紧张素转化酶基因的插入／缺失（I／D）多态性与原发性高血压的关系。方法 对941名开滦集团公司职工进行10年的纵向研究，应用聚合酶链反应进行血管紧张转化酶基因分型检测。结果 血管紧张素转化酶基因型Ⅱ，ID，DD三组人群10年中收缩压，舒张压数值的变化及高血压患病率的变化无统计学意义（P＞0．05）。结论 血管紧张素转化酶基因的I／D多态性与原发性高血压无关。     

血管紧张素转换酶基因多态性与原发性高血压的关系

目的：探讨中国人血管紧张素转换酶（ＡＣＥ）基因的插入／缺失（Ｉ／Ｄ）多态性与原发性高血压（ＥＨ）发病的相关性。方法按ＷＨＯ标准确诊的ＥＨ患者６８例,正常对照组６２例。用多聚酶链式反应（ＰＣＲ）和琼脂糖电泳技术,检测两组个体ＡＣＥ基因的Ｉ／Ｄ多态性。结果高血压组与正常对照组检测出３例基因Ⅱ、ⅠＤ和ＤＤ,频率分布分别为０．４８、０．３７、０．１５和０．３９、０．４８、０．１３,Ｉ、Ｄ等位基因频率分别为     

血管紧张素转换酶基因多态性和血管紧张素Ⅱ受体-1基因多态性与原发性高血压

目的探讨血管紧张素转换酶(angiotensin converting enzyme ,ACE)基因多态性和血管紧张素Ⅱ受体-1 (AT1R)基因多态性与原发性高血压(Essential Hypertension, EH)的关系,以及这两种基因多态性对于EH的发病是否有协同作用.方法对740名开滦集团公司职工进行10年的纵向研究,应用聚合酶链反应和限制性酶切方法检测ACE基因第16位内含子插入/缺失(I/D)多态性分布及AT1R基因A1166C多态性分布.结果 10年前或10年后EH组的ACE各基因型及等位基因频率与同期正常血压组比较无显著差异.10年前或10年后EH组的AT1R各基因型及等位基因频率与同期正常血压组比较无显著差异.10年前或10年后EH组中同时具有DD基因型和AC基因型的频率分布与同期正常血压组比较均无显著差异.10年前或10年后的男性EH亚组中,同时具有DD基因型和AC基因型的频率分布与同期正常血压组比较有统计学差异.结论血管紧张素转换酶基因的I/D多态性和血管紧张素Ⅱ受体-1基因A1166C多态性与原发性高血压无关,DD基因型和 AC基因型联合作用时对男性原发性高血压的发生可能有协同作用.     

血管紧张素转化酶基因多态性与原发性高血压的关系

目的研究血管紧张素转化酶（ＡＣＥ）基因的插入／缺失（Ｉ／Ｄ）多态性与原发性高血压的关系。方法应用ＰＣＲ的方法分别检测７２例原发性高血压患者和９３例正常血压组的ＡＣＥ基因第１６内含子的Ｉ／Ｄ多态性。结果共得到３种基因型：纯合缺失型（ＤＤ），纯合插入型（Ｉ），杂合型（ＩＤ）。原发性高血压患者Ｄ等位基因的频率（０．６２）高于健康对照组（０．４８）（Ｐ＜０．０５）。结论ＡＣＥ基因的Ｉ／Ｄ多态性可能与原发性高血压有关。     

原发性高血压患者血管紧张素转化酶和血管紧张素受体基因多态性的研究

目的　探讨血管紧张素转化酶 ( ACE)及血管紧张素 - 1型受体 ( AT1 R)基因多态性与原发性高血压 ( EHT)的关系。方法　应用聚合酶链反应及 PCR加酶解方法检测 1 50例健康人 ( NT)及 1 52例 EHT患者 ACE I/ D基因多态性的 ACE及 AT1 R A1 1 6 6 C突变。结果　 EHT组ACE I/ D基因多态性等位基因频率 I为 0 .50 ,D为 0 .50 ,D等位基因频率及基因型频率显著高于 NT组 ( P<0 .0 5) ;而两者之间的 AT1 R A1 1 6 6 C的C等位基因频率差异无显著性 ( P>0 .0 5)。结论　 ACE基因可能是 EHT的重要遗传因素 ,AT1 R基因 A1 1 6 6 C多态性与 EHT无关     

血管紧张素转换酶基因多态性与原发性高血压之间的关系

目的探讨中国人群中血管紧张素转换酶基因（ＡＣＥ）多态性与原发性高血压之间的关系。方法应用多聚酶链（ＰＣＲ）技术检测ＡＣＥ基因１６含子中２８７ｂｐＤＮＡ片段的插入／缺失（Ｉ／Ｄ）多态性；对７０例原发性高血压患者与４５例正常对照组之间进行比较。结果在原发性高血压组Ｄ等位基因频率（０．５５）高于正常对照组０．４３，但统计学并无意义，在有高血压家族史患者中，Ｄ等位基因频率０．５８高于对照组（Ｐ＜０．０５）。结论，表明在有家族史人群中ＡＣＥ基因多态性与原发性高血压具有相关性。     

藏族原发性高血压与血管紧张素转换酶基因多态性研究

高血压作为严重危害人类健康的复杂疾病，大量的研究结果奠定了肾素-血管紧张素系统在其发生机制中的重要研究地位，其相关基因也成为重要的高血压候选基因，其中最具争议的属血管紧张素转换酶(ACE)基因，近来两个大样本的研究证明ACE位点与血压变异相关。藏族作为我国各民族中高血压的高发人群，具有相对隔离人群遗传背景纯     

血管紧张素转化酶2基因多态性与原发性高血压的关系

目的研究血管紧张素转化酶2基因（ACE2-G8790A）单核苷酸多态性（SNP）与原发性高血压的关系。方法用PCR—RFLP及电泳分析法进行基因分型,SPSS软件分析各等位基因与原发性高血压的相关性。结果高血压患者与对照组的基因型、等位基因频率比较均有显著性差异（P=0．020,0．001）。高血压组GG、GA和AA基因型在女性中的分布频率分别为29．2％、42．4％和28．4％,女性对照组相应基因型的频率分别为29．3％、56．6％和14．1％,两组比较有显著性差异;G,A等位基因频率在高血压组分别为53．0％和47．0％,对照组相应的等位基因频率为63．3％,36．7％,两组比较差异有显著性（P〈0．01）。结论ACE2-G8790A基因多态性与原发性高血压相关。     

血管紧张素转换酶基因多态性与原发性高血压病

血管紧张素转换酶基因存在数种多态性标志,其第16内含子多聚酶链反应扩增产物可形成3种多态性：Ⅱ型、DD型及I／D型。DD型者血浆ACE浓度、血压高于I／D及Ⅱ型,D等位基因与高血压并发症密切相关,血管紧张素转换酶基因I／D多态性影响着原发性高血压病的发生、发展及预后。     

血管紧张素转换酶基因多态性与原发性高血压靶器官损害

血管紧张素转换酶 (ACE)基因是心血管系统的重要候选基因。 ACE基因多态性与原发性高血压心、脑、肾的并发症密切相关 ,ACE D等位基因是高血压靶器官损害的独立危险因子之一。检测 ACE基因型有利于原发性高血压患者高危人群的筛选。     

血管紧张素转换酶基因插入/缺失多态性与维吾尔族人群高血压病的关系

目的探讨血管紧张素转换酶基因的插入/缺失多态性与新疆维吾尔族人群高血压病之间的关系。方法应用聚合酶链反应对361例维吾尔族高血压病患者和400例正常血压者的血管紧张素转换酶基因16内含子插入/缺失多态性进行检测,测定血清总胆固醇、甘油三酯、血糖和总胆红素等生物化学指标,Logistic回归分析各基因型和等位基因频率与新疆维吾尔族原发性高血压的关系。结果将维吾尔族人群用Logistic回归模型校正年龄、性别、肥胖指数、腰围、臀围、盐摄入量、血糖、甘油三酯及总胆固醇之后,血管紧张素转换酶基因插入/缺失多态性与高血压病的发生相关,偏回归系数β值为0.246(P=0.0302),携带突变型纯合子DD个体患高血压的风险为II基因型的1.51倍(P=0.038)。结论血管紧张素转换酶基因插入/缺失多态性与新疆维吾尔族人群高血压发病相关,DD基因型可能是维吾尔族人群高血压发病的风险因子。     

血管紧张素转化酶基因插入/缺失多态性与冠心病的关系

为探讨血管紧张素转化酶基因插入／缺失多态性与冠心病的关系，用多聚酶链反应方法检测79例冠心病患者和68例健康人血管紧张素转化酶基因第16内含子中长度为287bP碱基片段的插入／缺入情况、按其存在与否将研究对象分为缺失型纯合子、插入型纯合子和杂合子，同时检测血清血管紧张素转化酶活性。结果发现冠心病组中缺失型基因频率显著高于对照组（P＜0．05），缺失型等位基因频率较对照组亦明显增高（P＜0．05）。对照组与冠心病组间血清血管紧张素转化酶活性比较无明显差别，但两组内不同基因型之间血管紧张素转化酶活性均存在显著差别，缺失型最高，插入型最低。以上结果提示，血管紧张素转化酶基因插入／缺失多态性与冠心病有关，缺失型可能是冠心病发生的危险因素之一，血管紧张素转化酶基因缺失型者冠心病的发生可能与其较高的血清转化酶水平有关。     

缺失型血管紧张素转换酶基因与心肌梗塞之间相关性的研究

本文采用PCR技术对91例心肌梗塞患者及132例正常对照者的血管紧张素转换酶（ACE）基因插入／缺失多态进行检测，结果显示：心肌梗塞组ACE基因中缺失型（DD型）分布（30％）明显高于正常对照组（17％）P＜0．05；心肌梗塞组缺失型等位基因频率（0.495）也明显高于对照组（0．356）P＜0．05。结果表明：缺失型ACE基因多态可能是中国人心肌梗塞的一个危险因素。     

山东籍汉族血管紧张素转换酶基因多态性与高血压左室肥厚的相关研究

目的研究山东籍汉族人ＡＣＥ基因Ｉ／Ｄ多态性与高血压病及左室肥厚与重构的关系。方法应用ＰＣＲ技术分别测定山东籍汉族人中６８例高血压病患者和７８例健康人的ＡＣＥ基因型,并对高血压病患者进行二维超声引导的Ｍ型超声检查。结果高血压病组ＡＣＥ基因ＤＤ基因型频率和Ｄ等位基因频率与对照组无显著性差异,但经纠正其它因素影响后,高血压病组ＤＤ型患者左室重量指数和室壁相对厚度均高于ＩＩ型患者（Ｐ＜０．０５）,经多元线性逐步回归分析,ＡＣＥ基因型与左室重量指数和室壁相对厚度均独立相关（总Ｒ２分别为０．３６和０．４９）。ＡＣＥ基因型分别可解释左室重量指数和室壁相对厚度总变异的３．７６％和２％。结论ＡＣＥ基因Ｉ／Ｄ多态性可能与山东籍汉族人高血压病发生无关联,但却是高血压病患者左室损害的新的独立危险因素     

血管紧张素转化酶I/D多态性与脑血管疾病的相关性

血管紧张素转化酶是一种可以催化血管紧张素Ⅰ转化为血管紧张素Ⅱ的蛋白酶.血管紧张素Ⅱ拥有比血管紧张素Ⅰ更强的活性,能使全身小动脉收缩进而升高血压,同时还具有刺激肾上腺皮质分泌醛固酮的作用,醛固酮具有保钠、保水、排钾的功能,能影响体液的水-电解质平衡而对机体带来广泛的影响.血管紧张素转化酶还能作用于激肽释放酶-激肽系统,通过灭活缓激肽而使血管收缩,并使血管通透性下降、血管对刺激的反应增强.近年来的一些研究表明血管紧张素转化酶的多态性与脑血管病的发生密切相关,文章旨在对近年来这方面的相关文献做一综述.     

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.More than one hundred years have elapsed since 1898, when Tigerstedt and Bergman at Karolinska Institute observed that injection of a crude extract of rabbit kidney raised the blood pressure (BP) in dogs (1). The extract contained a substance with long-lasting pressure effects that they named renin. Curiously, however, this seminal observation remained almost unnoticed until 1934, when Goldblatt showed that clamping of a kidney artery induced hypertension in the dog, an effect associated with the release of a vasopressor substance in the ipsilateral renal vein (2). Demonstrating an enhanced release of pressure substances from damaged kidneys into the circulation provided a reasonable pathophysiologic explanation for the well-known association between kidney disease and arterial hypertension and revived the seminal intuition of Claude Bernard that an endocrine mechanism, the milieu interior, is involved in the regulation of the systemic BP. A few years later, the concept of a system specifically involved in BP control came to the light with discovery by Page and Braun-Menendez that renin is a peptidase that produces the vasoconstrictor peptide angiotensin II from the precursor angiotensinogen (3). Since then, multidisciplinary research involving clinical scientists, pathologists, biochemists, physiologists, molecular biologists, and, more recently, geneticists, allowed identifying and characterizing many other components of the renin-angiotensin system (RAS), including the angiotensin-converting-enzyme (ACE), and specific receptors for the main RAS effectors, such as angiotensin II and aldosterone (4–10). Even more important, it soon became evident that RAS, in addition to controlling the systemic BP, may also have many other effects. Navar and Rosivall showed that angiotensin II enhances the tone of the postglomerular arteriole (11), which induces glomerular hypertension and increases the filtration fraction (12), hemodynamic adaptations that in the long-term may cause glomerular damage and dysfunction (13). Angiotensin II may also induce mesangial and vascular cell hypertrophy (14) and sustain chronic inflammation, ischemia, and fibrosis in proteinuric kidneys (15).The awareness that chronic RAS activation could have a key role in widely diffused, highly invalidating and often fatal diseases, boosted research efforts aimed to better characterize the system and to guide the development of intervention strategies aimed to limit its effects on vessels and tissues. Along this line, a major contribution came from novel molecular biologic techniques that, since the early 1980s, allowed to clone the genes encoding for various components of the system, such as renin, ACE and angiotensinogen (AGT), as well as for angiotensin II receptors type 1 (AT1R) and type 2 (AT2R) DNA cloning allowed also to detect gene polymorphisms of several components of the RAS, which helped geneticists to better understand the complex relationships between RAS and disease. In 1990, Rigat et al. (16) first described the insertion (I)/ deletion (D) polymorphism of the ACE gene, a major locus that accounts for approximately 50% of the total phenotypic variance of circulating and tissue ACE. Subjects carrying the D allele were found to have increased systemic and renal ACE levels, whereas those with the II genotype had the lowest ACE expression (17). Evidence that ACE is a limiting factor for angiotensin II synthesis, and therefore for most of the systemic and renal effects of the RAS, pushed researchers to focus a large part of genetic analyses of the RAS on the study of ACE I/D polymorphism. Thus, over the last decade, several studies converged to indicate that risk for development and progression of diabetic (18) and nondiabetic (19–21) chronic renal disease, as well as of related cardiovascular complications (22), varies with different I/D genotypes.With the development of captopril, the ancestor of a new class of antihypertensive agents, the ACE inhibitors, developed with the specific objective of limiting uncontrolled RAS activation in renovascular disease, Ondetti et al. (23) paved the way to a series of pharmacologic studies that provided new and largely unexpected insights on the concert of RAS effects. Studies found that RAS inhibition may lower the BP in patients with ischemic kidney disease and in a large proportion of those with essential hypertension as well, including patients with low plasma renin activity (24). Moreover, with time, the area of application of RAS inhibitor therapy extended from arterial hypertension to left ventricular hypertrophy and congestive heart failure, prevention of stroke, atherosclerosis, atrial fibrillation, and prevention and treatment of chronic kidney disease. Evidence that RAS inhibitors can be effective even in patients without signs of activity of the system is a major challenge to explore the possibility that the pathophysiology of cardiovascular and renal disease(s) are somehow linked to the function of renin angiotensin axis. Better understanding of the complex interactions of the RAS with hemodynamic and metabolic abnormalities of patients with hypertension, diabetes or renal disease, as well as with genetic variants of other pathways possibly involved in target organ damage, will hopefully open novel perspective of therapy for these high-risk patients. Evaluating these interactions, however, is difficult: large and well-characterized patient populations with homogeneous genetic backgrounds and univocally defined and clinically relevant outcomes are needed to give enough power to the analyses and limit the risk of random data fluctuations. Moreover, studies must take into consideration the role of acquired and environmental factors that may vary from one experimental setting to the other and may confound data interpretation. Unfortunately, most of the studies performed so far failed to satisfy the above requirements, largely because of the too small sample size or the heterogeneity of studied populations; and this may explain why data on the role of the RAS, and in particular of the ACE gene, in human disease were often inconclusive and sometimes even conflicting between different studies.Thus, our major task was to provide a critical overview of available evidence, trying to focus on most robust findings and, where possible, clean available information from unreliable or misleading data. We also discussed less solid data on other genetic factors that, combined with different ACE I/D genotypes, may contribute to the large interindividual variability in disease susceptibility and treatment response. Patients with diabetic and nondiabetic renal disease were treated separately to assess whether the same genetic factors may play a similar or different role in these two clinical settings. On the contrary, dissecting data on type I from those on type II diabetics was often difficult because many studies considered these patients together and only occasionally provided aggregate data in the two populations analyzed separately. We focused on papers considering microalbuminuria or macroalbuminuria, proteinuria, kidney function, and end-stage kidney disease (ESKD) as outcome variables. Relevant studies were retrieved by a literature search performed in MEDLINE (from 1996 to most recent) and EMBASE (from 1980 to most recent) by using specific key words according to considered genetic (RAS polymorphisms), disease (diabetic nephropathy, nondiabetic nephropathy) and drug categories (ACE inhibitors, angiotensin II receptor antagonism [ARA]). Randomized clinical trials were identified and selected for the meta-analysis according to the search strategy developed for the Cochrane Collaboration. Data on renal transplant patients were not considered.