血管紧张素转换酶基因多态性与中国人冠心病的关联研究

目的 探讨血管紧张素转换酶（ＡＣＥ）基因多态性在中国人冠心病发生发展中的作用。方法 应用聚合酶链反应技术和遗传学方法，测定１５９例中国汉族正常人，１４８例冠心病患者的ＡＣＥ原因插入／缺失（Ｉ／Ｄ）多态性频率。结果 （１）中国汉族正常人ＤＤ，ＩＤ，Ⅱ基因型频率分别为０．１５７，０．５３５和０．３０８，（２）冠心病组及其心肌梗塞，心绞痛亚组ＡＣＥ基因型分布与正常相比差异均有显著性（Ｐ〈０．０５），其Ｄ     

血管紧张素转换酶基因多态性与糖尿病和糖尿病肾病的关系

目的：研究血管紧张素转换酶（ＡＣＥ）基因多态性与Ⅱ型糖尿病（ＮＩＤＤＭ）发病及其与微血管合并症之间的关系。方法：应用ＰＣＲ方法对１３１例ＮＩＤＤＭ患者ＡＣＥ基因多态性进行了观察，并结合患者眼底和肾脏病变进行了分析。结果：ＮＩＤＤＭ患者ＤＤ型的发生频率明显高于正常人（Ｐ＜０．０１），ＤＤ型与ＮＩＤＤＭ的发生明显相关（ＯＲ＝４．２６，９５％可信限为１．９４８～９．３１４），ＮＩＤＤＭ患者伴眼底病变者ＤＤ型的发生频率明显高于无眼底病变的患者（Ｐ＜０．０５）。ＤＤ型与ＮＩＤＤＭ患者眼底病变的发生明显相关（ＯＲ＝４．６６７，９５％可信限为１．４１４～１５．４０）。ＮＩＤＤＭ患者伴肾病者ＤＤ型的发生频率明显高于无肾病患者（Ｐ＜０．０５），ＤＤ型与糖尿病肾病的发生明显相关（ＯＲ＝３．６３６，９５％可信限为１．１６８～１１．３２３）。结论：ＡＣＥ基因ＤＤ型与ＮＩＤＤＭ易感性相关，ＮＩＤＤＭ患者携带ＤＤ型者易罹患糖尿病眼底病变和糖尿病肾病。     

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。     

血管紧张素转化酶基因的插入／缺失多态性与心肌梗塞关系的研究

本研究运用ＰＣＲ技术对我国人１１６例心肌梗塞（ＭＩ）和１０３例健康作对照的血管紧张素转化酶（ＡＣＥ）基因插入／缺失多态性进行了检测，并与血清ＡＣＥ水平、ＭＩ发病、冠状动脉病变支数等指标进行比较。结果显示ＭＩ组缺失等位基因Ｄ频率０．４６和ＤＤ基因型频率０．２７显著高于对照组的０．３３和０．１２（分别为Ｐ＜０．０１，Ｐ＜０．０５）。同时发现缺失多态性与血清ＡＣＥ水平、ＭＩ组冠状动脉病变支数呈相关性。表明ＡＣＥ基因缺失多态性可能是我国人群ＭＩ发病的重要危险因素之一。     

血管紧张素转换酶基因多态性与狼疮性肾炎患者临床病理及预后…

为探讨血管紧张素转换酶（ＡＣＥ）基因多态性与狼疮性肾炎（ＬＮ）之间的关系，应用聚合酶链反应（ＰＣＲ）方法对１４４例ＬＮ患者和１５０名正常人ＡＣＥ基因多态性的分布进行了观察，并结合临床病理及随访资料进行了分析。发现ＬＮ患者ＤＤ基因型显著高于正常人（Ｐ〈０．０１），而Ⅱ基因型则明显低于正常人（Ｐ〈０．０１），ＤＩ基因型在两组人群中无统计学差异（Ｐ〉０．０５）；ＡＣＥ基因在ＤＩ基因型伴血尿、Ⅳ型ＬＮ、Ｌ     

血管紧张素Ⅰ转化酶基因多态性与老年人2型糖尿病肾病的关系

目的探讨血管紧张素Ⅰ转化酶（ＡＣＥ）基因插入／缺失多态性与老年人２型糖尿病（ＤＭ２）及糖尿病肾病合并肾功能不全（ＲＩ）的相关情况,同时观察血清ＡＣＥ水平与ＡＣＥ基因多态性及疾病的关系。方法对病程差异无显著性的７３例ＤＭ２患者、６８例ＲＩ患者及７２例健康对照者用ＰＣＲ方法进行了ＡＣＥ基因内含子１６插入／缺失多态性的检测,用紫外分光光度法测定了血清ＡＣＥ水平。结果ＲＩ组Ｄ等位基因频率为０．５３,ＤＤ基因型频率０．３２,与对照组（分别为０．３８、０．１５）比较差异有显著性（均为Ｐ＜０．０５）,ＤＤ基因型与ＩＩ基因型比较对ＲＩ的比数比为３．２９（Ｐ＜０．０１）;ＲＩ组血清ＡＣＥ水平显著高于对照组（Ｐ＜０．００１）。结论ＡＣＥ基因缺失多态性可能是老年人群ＲＩ的危险因素之一。     

血管紧张素转换酶基因多态性与高血压病合并左室肥厚相关性研究

目的：探讨血管紧张素转换酶（ＡＣＥ）基因插入／（Ｉ／Ｄ）多态性与原发性高血压合并左室肥厚的关系。方法：应用聚合酶链反应（ＰＣＲ）方法检测了７７ 例正常人,８０例无左室肥厚的高血压病病人,７４ 例高血压病合并左室肥厚患者的ＡＣＥＩ／Ｄ基因多态性。结果：高血压病合并左室肥厚组Ｄ等位基因频率为５１．６％ ,显著高于正常对照组（３５．６％ ,Ｐ＜ ０．０１）,及高血压无左室肥厚组（３９．３％ ,Ｐ＜ ０．０５）。结论：ＡＣＥ基因Ｄ等位基因型可能是中国高血压病患者左室肥厚的易感因素之一     

血管紧张素转换酶基因多态性与2型糖尿病患者脑梗塞的关系

目的探讨血管紧张素转换酶（ＡＣＥ）基因多态性与２型糖尿病脑梗塞间的关系。方法应用多聚酶链反应（ＰＣＲ）技术,对１０９名２型糖尿病患者及５２名正常对照者的ＡＣＥ基因插入／缺失（Ｉ／Ｄ）型多态性进行检测,并用Ｌｏｇｉｓｔｉｃ多元逐步回归,筛选出２型糖尿病患者脑梗塞的高危因素。结果（１）糖尿病总组ＡＣＥ基因型频率和等位基因频率与正常对照组无显著性差异（Ｐ＞０．０５）。（２）糖尿病脑梗塞组ＡＣＥ基因ＤＤ型和Ｄ等位基因频率显著高于非脑梗塞组（Ｐ＜０．０１）及正常对照组（Ｐ＜０．０５）。（３）多元逐步回归分析显示：ＡＣＥ基因ＤＤ型、Ｄ等位基因、脂蛋白（ａ）及年龄是糖尿病脑梗塞的独立危险因素,而ＡＣＥ基因ＩＩ型和Ｉ等位基因则为２型糖尿病脑梗塞的保护因子。结论ＡＣＥ基因Ｉ／Ｄ多态性与２型糖尿病脑梗塞的发病密切相关。ＡＣＥ基因     

葡萄糖转运蛋白基因多态性与糖尿病和糖尿病肾病的关系

目的：探讨葡萄糖转运蛋白（ＧＬＵＴ１）基因多态性与糖尿病及糖尿病肾病（ＤＮ）的关系。 方法：应用ＰＣＲ方法对１３１例Ⅱ型糖尿病（ＮＩＤＤＭ）患者ＧＬＵＴ１基因多态性与ＮＩＤＤＭ及ＤＮ发生之间的关系进行了观察，并结合患者体重指数（ＢＭＩ）和胰岛素敏感指数（ＩＳＩ）进行分析。 结果：①ＮＩＤＤＭ组患者Ｘｂａ Ｉ（＋／－）基因型的发生频率明显高于正常人群（６２％ｖｓ３３％，Ｐ〈０．０１），而Ｘｂａ Ｉ（     

血管紧张素转换酶基因多态性与糖尿病和糖尿病肾病…

目的：研究血管紧张素转换酶（ＡＣＥ）基因多态性与Ⅱ型糖尿病（ＮＩＤＤＭ）发病及其与微血管合并症之间的关系。 方法：应用ＰＣＲ方法对１３１例ＮＩＤＤＭ患者ＡＣＥ基因多态性进行了观察，并结合患者眼底和肾脏病变进行了分析。 结果：ＮＩＤＤＭ患者ＤＤ型的发生频率明显高于正常人（Ｐ〈０．０１），ＤＤ型与ＮＩＤＤＭ的发生明显相关（ＯＲ＝４．２６，９５％可信限为１．９４８￣９．３１４），ＮＩＤＤＭ患者伴眼底病变     

血管紧张素Ⅰ转化酶基因多态和2型糖尿病肾病相关性研究

血管紧张素Ⅰ转化酶（ＡＣＥ）基因多态和２型糖尿病肾病（ＤＮ）的关系。方法用ＰＣＲ技术检测１０２例中国汉族２型糖尿病患者ＡＣＥ基因Ｉ／Ｄ多态基因型。结果ＤＮ组（ｎ＝３６）和无ＤＮ组（ｎ＝４９）相比,Ｄ型等位基因和ＤＤ基因型糖频率升高（分别为５９．７％ｖｓ３８．８％,Ｘ＾２＝７．３０,３３．３％ｖｓ１２．２％,Ｘ＾２＝５．５３）,有显著性差异（Ｐ〈０．０５）,病程≤５年合并ＤＮ组（ｎ＝１１）与病程〉５     

Angiotensin converting enzyme (ACE) gene polymorphism increases the susceptibility of diabetic nephropathy in Western Indian Type 2 diabetic patients

Angiotensin-converting enzyme (ACE) gene has been associated with the pathogenesis and progression of chronic kidney diseases. Diabetic nephropathy has become leading cause of renal end stage disease (ESRD). An I/D polymorphism of angiotensin-converting enzyme (ACE) gene has been suggested as one of the risk factors for the progression of diabetic nephropathy. We analyzed the genotype and allele frequency distribution of ACE gene in 166 Type 2 diabetic patients without any complication (T2DM), 61 with diabetic nephropathy (DN), 50 with non-diabetic nephropathy (NDN) and 50 healthy individuals from western Indian population. ACE genotype was analyzed by PCR method. The D allele distribution for the ACE I/D polymorphisms was not significantly different between control group and patients with T2DM without any complication (41.0% vs. 45.2%, P?=?0.461) and between control subjects and patients with non-diabetic nephropathy (NDN) (41.0% vs. 44.0%, P?=?0.668). Frequency of the D allele (63.9% vs. 45.2%, P?<?0.001) and DD genotype (I allele noncarrier) (44.3% vs. 25.3%, P?=?0.006) of ACE gene was significantly higher in patients with diabetic nephropathy (DN) than in patients with T2DM without any complication. Results of the present study indicate that ACE gene polymorphism does not have significant influence on development of diabetes mellitus and nondiabetic nephropathy, whereas, the DD polymorphism in ACE gene has been associated with the development of diabetic nephropathy in the Western Indian population.     

Genetic polymorphism of renin-angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus.

In a hospital cohort study, we examined whether or not ACE (Angiotensin-I converting enzyme) and AGT (Angiotensinogen) gene polymorphisms were associated with the development of nephropathy in long-term Japanese insulin-dependent diabetes mellitus (IDDM) patients with or without proliferative retinopathy, and whether or not the polymorphisms were associated with an arteriosclerotic family history in first degree relatives of the patients. A total of 201 patients with IDDM for more than 10 years and 159 patients with IDDM for more than 15 years were randomly selected in our hospital. All patients received uniform diabetes management and were divided into three groups, no nephropathy, incipient nephropathy and clinical nephropathy groups. There were no differences in clinical characteristics excluding urinary albumin to creatinine ratio and systolic blood pressure between the three groups. ACE I/D polymorphism was related to plasma ACE activity, but there were no associations between ACE I/D polymorphism and the development of diabetic nephropathy, nor was renal deterioration observed in patients with proliferative retinopathy even in those with a history of diabetes for more than 15 years. The AGT polymorphism did not have an additive effect on the association between ACE polymorphism and the development of diabetic nephropathy in patients with or without retinopathy. Development of diabetic nephropathy in the patients with or without proliferative retinopathy did not result in ACE or AGT polymorphisms. On the other hand, the ACE DD genotype was associated with a family history of ischemic heart disease in first degree relatives (X2 score = 9.04, P < 0.05). ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.     

Angiotensin Converting Enzyme Gene Polymorphism in Iranian Patients with Type 2 Diabetes

Background: Angiotensin I converting enzyme (ACE) is a Zinc metalloproteinase, converts Ang-I to Ang- II, a pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. Objective: To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. Methods: 170 patients (85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy) and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction (PCR) utilizing specific primers. Results: The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients (30.6% vs. 20%, P =0.157) and the control group (30.6% vs. 14.3%, P=0.006). The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% (P=0.19) and control subjects 37.3% (P =0.001). Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. Conclusion: It is concluded that the DD genotype and/or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy.     

血管紧张素转换酶基因多态性与高血压微量蛋白尿的关系

为研究血管紧张素转换酶基因插入/缺失（I/D）多态性与高血压微量蛋白尿的关系。应用聚合酶链反应方法扩增50例正常人，50例高血压伴有微量蛋白尿患者和49例高血压不伴有微量蛋白尿患者的白细胞血管紧张素转换酶基因上287bp片段，根据插入（Ⅰ）或/缺失（D）来判断其多态性，用放射免疫法测定所有对象的尿微量白蛋白。结果发现，微量蛋白尿组与健康对照组相比，其D等位基因及DD基因型显著升高。微量蛋白尿组与单纯高血压组相比，其D等位基因及DD基因型显著程式高。单纯高血压组与健康对照组相比，血管紧张素转换酶基因型和等位基因频率无显著性差异。以上提示，血压紧张素转换酶基因多态性与高血压微量蛋白尿有关联性，DD基因型可能与高血压早期肾脏损害有关。     

Evaluation of risk factors for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control

Summary Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM). Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA_1c values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA_1c values. However, mean long-term HbA_1c values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure. The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA_1c values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy. [Diabetologia (1997) 40: 327–331] Received: 1 July 1996 and in final revised form: 20 November 1996     

Insertion/deletion polymorphism in the angiotensin-l-converting enzyme gene is associated with coronary heart disease in IDDM patients with diabetic nephropathy

Summary Insulin-dependent diabetic (IDDM) patients with diabetic nephropathy have a highly increased morbidity and mortality from coronary heart disease. An insertion (I) /deletion (D) polymorphism in the angiotensin-I-converting enzyme (ACE) gene has been shown to be associated with coronary heart disease. Therefore, we have investigated the role of this ACE/ID polymorphism in 198 IDDM patients with diabetic nephropathy and 190 normoalbuminuric IDDM patients. The prevalence of myocardial infarction and other coronary heart disease was significantly elevated in patients with nephropathy, 19 % (38/198) vs 8 % (15/190), p < 0.001. In the nephropathic group 12 of 63 (19 %), 23 of 95 (24 %), and 3 of 40 (7.5 %) patients with the DD, ID and II genotypes, respectively had a history of coronary heart disease, II vs DD and ID, p < 0.05 when compared to nephropathic patients without coronary heart disease. Multiple logistic regression analysis of the risk factors associated with coronary heart disease in univariate analysis revealed that the II genotype acts as an independent protective factor against coronary heart disease, odds ratio II/DD + ID 0.27 (95 % confidence interval 0.07–0.97, p < 0.05). There was no difference in genotype or allele frequency (D/I) between patients with and without nephropathy, 0.56/0.44 in both groups, but plasma ACE concentration was elevated in patients with nephropathy 609 (151–1504) ng/ml as compared to patients with normoalbuminuria, 428 (55–1630) ng/ml, p < 0.001. We suggest that ACE/ID polymorphism may influence the frequency of life-threatening cardiac complications in IDDM patients suffering from diabetic nephropathy, a condition characterized by increased plasma ACE concentration. [Diabetologia (1995) 38: 798–803] Received: 10 October 1994 and in revised form: 20 December 1994     

Association between a polymorphism in the angiotensin-converting enzyme gene and microvascular complications in Japanese patients with NIDDM

Summary The relationship between diabetic nephropathy and an insertion (I)/deletion (D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still under debate. The association of ACE gene polymorphism with nephropathy and retinopathy was therefore examined in 362 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and 105 healthy control subjects. Distribution of the ACE genotype did not differ between healthy control subjects and diabetic patients without complications. However, the frequency of the D allele was significantly higher in the diabetic subjects with nephropathy than in those without (0.32 in normoalbuminuric patients vs 0.44 in albuminuria patients with albuminuria) (²=7.7; p=0.006). There was no significant association between ACE genotype and retinopathy. These observations thus demonstrate a significant association of the ACE gene polymorphism with nephropathy, but not with retinopathy, in Japanese patients with NIDDM.Abbreviations ACE Angiotensin-converting enzyme - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - UAI urinary albumin index - PCR polymerase chain reaction     

ACE基因I/D多态性与系统性红斑狼疮肾脏易感性关系的研究

研究血管紧张素转换酶基因Ｉ／Ｄ多态性与系统性红斑狼疮肾脏易感性的关系。方法用ＰＣＲ法和比色法分别测定５８例ＳＬＥ患者和４０例正常人的ＡＣＥ基因型和血清ＡＣＥ活性。结果确诊ＳＬＥ时临床有肾脏受累表现组ＡＣＥ基因ＤＤ型和Ｄ等位基因分布频率明显高于组，且ＤＤ型、ＤＩ型者血清ＡＣＥ活性前者明显于高于后者。     

ACE基因插入/缺失多态与国人肺血栓栓塞症的关联研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(ID)多态是否与肺血栓栓塞症存在关联,D等位基因是否增加国人肺血栓栓塞的危险。方法放射性核素肺通气-灌注扫描和(或)超高速CT检查并结合临床资料确诊的肺血栓栓塞症患者72例及性别、年龄匹配的健康对照者72名。调查静脉血栓形成和肺栓塞相关危险因素。酚-氯仿法提取基因组DNA,聚合酶链反应(PCR)鉴定ACE基因I/D多态点基因型。结果(1)病例组外伤、手术史及下肢静脉炎、静脉曲张发生率显著高于对照组,肺血栓栓塞家族史、心血管疾病家族史、口服避孕药、吸烟及饮酒史两组间差异无显著性。(2)健康对照组I、D等位基因频率分别为66％和34％,基因型分布符合Hardy-Weinberg平衡。Ⅱ、ID和DD基因型及I、D等位基因频率在病例和对照组差异无显著性。(3)进一步分别按显性、隐性和加性作用方式探讨ACE基因I/D多态与肺血栓栓塞症的关系,发现DD基因型个体肺栓塞危险显著增加(OR=2.51,P＜0.05),提示D等位基因为隐性作用方式。(4)将肺血栓栓塞患者按有无明确静脉血栓形成及肺栓塞环境诱因分组,结果显示无明确环境诱因组DD基因型频率显著高于对照组(27.1％vs14.3％;OR=2.64,P＜0.05),而有明确环境诱因组与对照组相比DD基因型频率差异无显著性。将肺血栓栓塞患者按是否合并下肢静脉血栓形成分组,结果显示肺栓塞合并下肢静脉血栓形成组DD基因型频率显著高于健康对照组(32.4％vs14.3％;OR=3.36,P＜0.05),单纯肺栓塞组与健康对照组比较差异无显著性。结论ACE基因I/D多态与国人肺血栓栓塞有关,D等位基因为隐性作用方式。DD基因型显著增加无明确静脉血栓形成及肺栓塞环境诱因个体肺栓塞危险;有下肢静脉血栓形成病史的DD基因型个体肺栓塞危险亦显著增加。