Determination of human angiotensin converting enzyme (ACE) gene polymorphisms in erectile dysfunction: frequency differences of ACE gene polymorphisms according to the method of analysis.

The D polymorphism of angiotensin converting enzyme (ACE) gene has been found to be associated with various diseases, and ACE may also be involved in the pathogenesis of erectile dysfunction. On the other hand, interpretation of the data on the association of DD genotype with various diseases is controversial, due to methodological and technical variations in detection of the polymorphisms. We investigated a possible association between the DD genotype and erectile dysfunction in a Korean population, and compared the frequency of ACEgenotypes using our multiplexed PCR method with those based on the conventional PCR method in a sample of erectile dysfunctional and control subjects. There was significant difference in the distribution of ACE genotypes between the erectile dysfunctional (conventional PCR) and the control subjects (multiplexed PCR) (chi2=7.395, p<0.05), but there was no significant difference in the distribution of the genotypes between both groups (chi2=0.815, p>0.05) when our multiplexed PCR method was used. Therefore our results suggest that especially the conventional PCR method for ACE gene polymorphism may require careful control and may need repeated testing to verify the insertion deletion (ID) heterozygotes, and that a multiplexed PCR method can markedly increase the detection rate of the I allele in ID heterozygotes. No association was found between I/D polymorphism and erectile dysfunctional subjects in the Korean population studied.     

The insertion/deletion polymorphism of the ACE gene is related to insulin sensitivity in overweight women

OBJECTIVE: The ACE insertion/deletion (I/D) polymorphism has been identified as a genetic risk factor for coronary heart disease (CHD). The deletion (D) allele of the ACE gene may be associated with higher insulin sensitivity. Individuals who are homozygous for the DD allele have higher ACE levels and possibly more angiotensin II, which, when infused exogenously, causes an increase in insulin sensitivity. The purpose of this study was to investigate the association of the I/D polymorphism of the ACE gene with insulin sensitivity and CHD risk factors. RESEARCH DESIGN AND METHODS: The study included 66 women (ages 57 +/- 1 years) who were overweight or obese (means +/- SEM, BMI = 33 +/- 1 kg/m(2)) and sedentary (VO(2max) = 19.6 +/- 0.4 ml. kg(-1). min(1)). Total body fat mass and percent fat were determined by dual-energy X-ray absorptiometry, and abdominal fat was by computed tomography. Insulin sensitivity was measured during the last 30 min of 3-h hyperinsulinemic-euglycemic clamps (40 mU. m(-2). min(-1)). Comparisons were made among women with the II (n = 9), ID (n = 36), and DD (n = 21) genotypes. RESULTS: Age, percent body fat, waist-to-hip ratio, visceral and subcutaneous abdominal fat areas, plasma lipid levels, and systolic and diastolic blood pressures did not differ by ACE genotype. Fasting glucose and 2-h glucose levels were similar among genotypes, but fasting plasma insulin levels were lower in DD women than in ID women (P < 0.05). Glucose utilization was higher in women with the DD genotype than in women with the II genotype (53.1 +/- 3.9 vs. 36.0 +/- 3.8 micromol. kg(-1) FFM. min(-1), P = 0.01) and was higher in ID women than in II women (48.5 +/- 2.5 micromol. kg(-1) FFM. min(-1), P = 0.04). CONCLUSIONS: These data suggest that the I/D polymorphism is not associated with risk factors for CHD in overweight sedentary women; however, women who are homozygous for the D allele of the ACE gene are more insulin sensitive, whereas women who are homozygous for the I allele of the ACE gene have greater insulin resistance and potential risk for type 2 diabetes.     

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7+/-18.6 units/l compared with 22.8+/-12.8 units/l; P=0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40-5.71; P<0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04-0.69; P=0.014; and patients with AMI, OR=0.21; 95% CI, 0.061-0.749; P=0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II (P=0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09-2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.     

Angiotensin-converting enzyme genotype in blacks with diabetic nephropathy: effects on risk of diabetes and its complications.

OBJECTIVE: Among blacks, we have observed that diabetic nephropathy (DN) is a more frequent primary cause of end-stage renal disease (ESRD) in women (approximately 50%) than in men (< 20%). In this study, we consider the role of the angiotensin-converting enzyme (ACE) polymorphism in determining this gender discrepancy and its role in the course of DN. METHODS: ACE genotype (I = insertion, D = deletion) was determined in consecutive consenting patients with type 2 diabetes mellitus and DN. Charts were subsequently reviewed for renal survival and its determinants (end point: time to ESRD from first clinic visit). RESULTS: Fifty-four patients (46 blacks) who had DN and were pre-ESRD consented: II = 6, ID = 31, and DD = 17. The allele frequency for D was approximately . 61 versus .39 for the I allele and did not differ by gender. Renal disease at presentation to the renal clinic was significantly worse in II. Twenty-one patients reached ESRD (II = 4, ID = 13, DD = 4; chi2 not significant), but ACE genotype had no significant effect on renal survival. Initial serum creatinine and blood pressure over follow-up independently predicted renal survival. Among blacks reaching ESRD, the presence of the D allele was associated with higher blood pressures. Patients without a family history of diabetes (chi2, p = .01) or diabetic retinopathy (chi2, p = .02) were more likely to have the DD genotype. CONCLUSIONS: The gender discrepancy observed in rates of ESRD owing to DN in blacks is not likely dependent on ACE genotype. The effects of ACE genotype on renal disease progression were not significant; however, patients with diabetic nephropathy and DD genotype were less likely to have traditional risk factors for diabetes or diabetic nephropathy.     

血管紧张素转化酶基因I/D多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征患者左心室肥厚的关系

目的探讨血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与维吾尔族高血压合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者左心室肥厚(LVH)的关系。 方法选取2015年1月至2016年12月于新疆医科大学第一附属医院高血压科首诊住院,且未服用血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)类降压药物的维吾尔族高血压合并OSAHS患者,共72例,行多导睡眠呼吸监测、动态血压、心脏彩超等检查,聚合酶链式反应(PCR)和琼脂糖凝胶电泳技术测定ACE基因多态性。根据左心室质量指数分为左心室肥厚组(LVH组,n＝24)和非左心室肥厚组(NLVH组,n＝48),比较两组间基因型及基因频率的差异,使用多因素Logistic回归分析左心室肥厚的影响因素。 结果高血压合并OSAHS患者LVH组ACE基因型频率分别为：II(37.50%),ID(20.83%),DD(41.67%),等位基因频率分别为：I(48.00%),D(52.00%),与NLVH组[II(47.92%),ID(37.50%),DD(14.58%),I(67.00%),D(33.00%)]比较,差异有统计学意义(χ²＝6.75,4.70;均P<0.05);对左心室肥厚影响因素进行多因素Logistic回归分析,呼吸暂停低通气指数(AHI)(OR＝6.20,95%CI：1.44～26.77;P<0.05)、DD基因型(OR＝4.61,95%CI：1.05～20.31;P<0.05)是维吾尔族高血压合并OSAHS患者发生LVH的独立危险因素。 结论ACE基因I/D多态性与维吾尔族高血压合并OSAHS患者发生LVH有关,其中DD基因型维吾尔族患者更易发生LVH。     

蒙古族人群血管紧张素转换酶基因多态性与高血压的关系

背景有关血管紧张素转换酶基因多态性与高血压关系的研究已有报道,但在蒙古族人群中尚不十分清楚.蒙古族是高血压患病率较高的民族,因此有必要探讨蒙古族人群中血管紧张素转换酶基因多态性与高血压的关系.目的探讨蒙古族人群血管紧张素转换酶基因多态性与高血压的关系.设计采用现况调查的方法.地点和对象选择内蒙古自治区通辽市科左后旗朝鲁吐苏木作为本研究现场,所有研究对象均为在此长期居住的蒙古族居民.共获得有高血压家族史的高血压者51例、血压正常者32例和没有高血压家族史的高血压者64例、血压正常者85例.干预应用聚合酶链式反应检测血管紧张素转换酶基因的插入/缺失多态性.主要观察指标血管紧张素转换酶多态性基因型频率和I、D等位基因频率.结果血管紧张素转换酶基因的三种基因型(II,ID,DD)在4组人群间的分布差异无显著性意义(P＞0.1).在4组人群中均表现出ID基因型频率最高,其次为Ⅱ基因型,DD基因型频率最低.I,D等位基因在4组人群间的分布也差异无显著性意义(P＞0.1).在4组人群中I等位基因频率均高于D等位基因频率.结论血管紧张素转换酶基因I/D多态性与蒙古族高血压的发生无关联.     

血管紧张素Ⅰ转换酶基因多态性与妊娠高血压综合征的关系

目的:探讨血管紧张素Ⅰ转换酶(ACE)基因多态性与妊娠高血压综合征(妊高征)发病的关系。方法:应用多引物PCR技术检测120例妊高征患者(妊高征组,其中轻度29例、中度31例、重度60例)及110例正常孕妇(对照组)的ACE基因多态性。结果:妊高征组孕妇ACE基因中的II、ID、DD基因型频率分别为20.8%、37.5%、41.7%。对照组孕妇ACE基因中的II、ID、DD基因型频率分别为44.5%、29.1%、26.4%。两组孕妇的DD基因型及D等位基因频率比较,差异有显著性(P<0.05)。妊高征组轻度与重度患者的DD基因型比较,差异有显著性(P<0.05)。回归分析表明,DD基因型及D等位基因与妊高征发病相关。结论:ACE基因中DD基因型是妊高征的易感基因,II基因型是妊高征的保护基因。     

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.     

汉族人群血管紧张素转换酶基因插入/缺失(I/D)的遗传多态性

背景:血管紧张素转换酶是肾素-血管紧张素-醛固酮系统的重要组成部分,血管紧张素转换酶基因第16内含子内存在一个287bp的Alu序列的插入/缺失(I/D)多态性,与心血管疾病、IgA肾病等疾病的发生具有一定的相关性。目的:分析汉族人群血管紧张素转换酶基因插入/缺失(I/D)多态性的分布,并与已知的其他种族人群进行比较。设计:以健康汉族人为观察对象的观察性实验。单位:江苏省临床免疫学重点实验室,苏州大学附属第一医院检验科,江苏大学医学技术学院检验系。对象:受检者为2005-12/2006-01苏州大学附属第一医院门诊健康体检者241名,男152名,女89名,平均年龄(27±8)岁,均为无血缘关系的苏州地区汉族人,经临床及实验室检查确认排除肝、肾、内分泌、心脑血管疾病。方法:应用聚合酶链反应检测了241名汉族健康体检者血管紧张素转换酶基因I/D多态性等位基因的基因型,并采用荧光标记末端终止法对基因型为D/D、I/I的PCR纯化产物进行DNA测序确认。主要观察指标:血管紧张素转换酶基因I/D基因型,等位基因频率以及与其他种族人群的比较。结果:241名受检者全部进入结果分析。①血管紧张素转换酶的基因型表现为缺失纯合子(DD)、插入纯合子(II)以及缺失和插入杂合子(DI),等位基因D较等位基因Ⅰ缺失一段287bp的核苷酸,即Alu序列。②II,ID,DD基因型频率分别为46.1%,41.5%,12.4%;等位基因I,D频率分别为66.8%,33.2%。③日本人与汉族人群血管紧张素转换酶基因型分布相似,均以II型最常见,DD型最少;欧美人群以ID居多,II型较少。汉族人群与日本人及欧美人群血管紧张素转换酶基因型频率的分布具有种族差异性。与其他各民族人群比较,汉族人群等位基因I显著高于上述各民族(χ2=105.55,P<0.01),等位基因D明显较低(χ2=87.54,P<0.01)。结论:血管紧张素转换酶基因多态性具有种族差异性。了解不同种族人群间血管紧张素转换酶基因多态性的遗传特点,是研究血管紧张素转换酶基因I/D多态性与疾病相关性的基础和前提。     

Relationship between glomerular hyperfiltration and ACE insertion/deletion polymorphism in type 1 diabetic children and adolescents

OBJECTIVE: Glomerular hyperfiltration may predict diabetic nephropathy in type 1 diabetes, and some studies suggest that the ACE D allele is associated with diabetic nephropathy. The aim of this study was to examine a possible relationship between glomerular hyperfiltration and ACE insertion/deletion (I/D) polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted to examine the relationship between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1 diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA1c 9.5 +/- 1.9%). Glomerular hyperfiltration (defined as a glomerular filtration rate [GFR] > or = 135 ml.min-1. 1.73 m-2 and by 51Cr-labeled EDTA plasma disappearance technique) and ACE I/D genotypes and plasma levels (enzyme-linked immunosorbent assay [ELISA] method) were determined. RESULTS: Of the patients, 29 (38%) displayed glomerular hyperfiltration. An association between glomerular hyperfiltration and ACE (I/D) polymorphism was observed (chi 2 = 7.09, P = 0.029) because of a reduced proportion of DD genotypes among patients with glomerular hyperfiltration (4 vs. 19; chi 2 = 6.03, P = 0.014) and not because of an excess of the II genotype (5 vs. 9; chi 2 = 0.04, P = 0.83). Age, diabetes duration, age at diabetes onset, and HbA1c were not different according to genotype. Patients with glomerular hyperfiltration had low plasma ACE levels, compared with those with normal glomerular filtration (457 +/- 157 vs. 553 +/- 186 micrograms/l; P = 0.027). CONCLUSIONS: These results suggest an unexpected association between glomerular hyperfiltration and ACE (I/D) polymorphism, characterized by a defect of the DD genotype among type 1 diabetic children and adolescents with glomerular hyperfiltration.     

Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic patients

We aimed to investigate the angiotensin-converting enzyme (ACE) gene polymorphism, ACE activity and their associations with diabetic complications in Turkish patients with type 2 diabetes mellitus. A total of 143 patients and 133 controls were screened for ACE gene I/D polymorphism by using polymerase chain reaction. Serum ACE activities were determined spectrophotometrically. There was no significant difference in the distribution of ACE I/D genotypes between patients and controls. The patients with DD genotype had a higher ACE activity than those with ID and II. Hypertensive diabetic patients with DD genotype had higher ACE activities than those with ID and II. There was no significant difference in the distribution of ACE I/D genotypes between patients with and without nephropathy, retinopathy and hypertension except for patients with and without neuropathy. In patients with DD genotype, creatinine clearance correlated with duration of diabetes. The grade of retinopathy was correlated with duration of diabetes in DD and ID genotypes. The highest ACE activity was measured in hypertensive diabetics with DD genotype. ID genotype was suggested to be a risk factor and II was suggested to be protective for diabetic neuropathy. The DD and ID genotypes might be a predictor for the development of retinopathy in relation to duration of diabetes.     

ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients

OBJECTIVE: Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 711 patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by PCR. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 World Health Organization classification. RESULTS: Of 711 patients with type 2 diabetes, 534 (75.1%) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype was 9.4, 11.5, and 15.4%, respectively, and in patients with type 2 diabetes, it was 68.6, 79.2, and 86.1%, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (P = 0.001). When pooling the control subjects with diabetic patients, the prevalence of metabolic syndrome in the whole study group with II, ID, and DD genotype was 37.9, 44.5, and 51.0%, respectively, and ACE I/D polymorphism was still significantly associated with metabolic syndrome (P = 0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD = 43.1/53.1/65.8%, P < 0.001) and albuminuria (36.0/44.6/50.6%, P = 0.018) and to have higher serum triglyceride levels (II, ID, and DD = 155 +/- 114, 170 +/- 140, and 199 +/- 132 mg/dl, respectively, P < 0.05). Control subjects with DD genotype were also found to have a higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD = 5.7/14.0/15.4%, P = 0.001), whereas the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling control with diabetic subjects, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD = 34.7/41.3/52.2%, P < 0.001) and albuminuria or more advanced nephropathy (20.3/28.9/33.1%, P < 0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 +/- 1.8 vs. 5.3 +/- 1.4 mg/dl, P < 0.01). CONCLUSIONS: The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome and suggests that the renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.     

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.     

Interaction between angiotensin-converting enzyme genotype and glycaemic control influences lipoprotein levels in type 2 diabetes mellitus

AIMS: To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes. PATIENTS AND METHODS: 109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction. RESULTS: The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21 +/- 0.25 g/l vs. ID + II: 1.04 +/- 0.27 g/l; P = 0.007). Significant correlations between glycated haemoglobin (HbA1c) and both apoB and cholesterol levels were found (r = 0.27; P < 0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r = 0.54; P < 0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA1c and the interaction of genotype DD with HbA1c were significant independent predictors of apoB (r2 = 0.17) and cholesterol levels. CONCLUSION: The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA1c level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.     

血管紧张素转换酶基因多态性与肝肾综合征相关研究

目的　探讨血管紧张素转换酶 (ACE)基因插入 /缺失 (I/ D)多态性与失代偿性肝硬化并发肝肾综合征 (HRS)之间的关系。方法　应用聚合酶链反应方法扩增 5 6例失代偿性肝硬化并发 HRS患者及 6 0例正常对照组 ACE基因上 DNA片断 ,根据 I/ D判断其多态性 ;同时各例均采血测丙氨酸转氨酶、天冬氨酸转氨酶、血清肌酐 (SCr)及尿素氮 (BU N)等指标 ,并测定肾小球滤过率 (GFR) ,比较不同基因型间上述指标的差异显著性。结果　 HRS患者各基因型及等位基因频率与对照组间差异均无显著性 (P均 >0 .0 5 ) ;I等位基因频率均显著高于 D等位基因频率 (P均 <0 .0 1)。正常对照组中 3种基因型频率间差异无显著性 (P>0 .0 5 ) ;HRS组中 II基因型频率显著高于 ID型及 DD型 (P均 <0 .0 5 )。 II基因型的 BU N与 SCr均显著高于 ID型及 DD型(P均 <0 .0 5 ) ,GFR显著低于 ID型及 DD型 (P均 <0 .0 5 )。结论　 ACE基因多态性与失代偿性肝硬化并发HRS的发生率有关 ,II基因型可能为失代偿性肝硬化易并发 HRS的遗传学方面因素 ;失代偿性肝硬化并发HRS患者中 ,II基因型个体的肾功能衰竭程度重于 ID型及 DD型。     

血管紧张素转换酶基因多态性与高血压病血管内皮纤溶障碍的关系

目的 :探讨 ACE基因 I/ D多态性与原发性高血压 (EH)及高血压血管内皮纤溶功能障碍间的关系。方法 :PCR检测 6 1例原发性高血压患者和正常对照组 2 8例的 ACE基因 I/ D多态性 ;发色底物法测 t- PA、PAI- 1活性 ,酶联免疫吸附双抗夹心法 (EL ISA)测 v WF含量。结果 :高血压组 DD基因型频率显著高于对照组 (P<0 .0 5 ) ,但 D等位基因频率分布在高血压组和正常组之间无差异性 (P>0 .0 5 )。高血压组 t- PA活性降低 ,PAI- 1活性、v WF含量升高 (P均 <0 .0 0 1)。高血压组 DD型 t- PA活性明显低于 ID、II型 (P<0 .0 0 1) ,而 ID、II型之间无统计学差异 (P>0 .0 5 ) ,DD型 PAI-1活性明显高于 ID、 型 (P<0 .0 0 1) ,而 ID、II型之间无统计学差异 (P>0 .0 5 ) ,v WF在 DD、ID、II型三者之间无明显差异 (P均 >0 .0 5 )。结论 :DD型是原发性高血压发病的危险因素。原发性高血压存在血管内皮损伤、纤溶功能障碍。t- PA、PAI- 1的变化与血管紧张素转换酶基因 I/ D多态性有关 ,DD基因型可引起纤溶功能紊乱。     

The link between angiotensin-converting enzyme genotype and pulmonary artery pressure in patients with COPD

OBJECTIVE: The insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of cardiovascular diseases. In patients with primary pulmonary hypertension, the homozygous ACE DD genotype is more prevalent than the non-DD genotype. However, the relationship of ACE gene polymorphism to secondary pulmonary hypertension remains unclear, and ethnicity may be one of the factors that can modulate the effects of ACE genotypes reported in different studies. We hypothesized that in patients with chronic obstructive pulmonary disease (COPD) the presence of the D allele in the ACE gene polymorphism is associated with increased pulmonary artery pressure (Ppa). PATIENTS AND METHODS: Bodyplethysmography was used to assess lung function in 66 consecutive patients with COPD; pulmonary artery pressures were determined using echocardiography. ACE gene I/D polymorphism was identified with the polymerase chain reaction. 118 healthy persons served as the control group. All patients and controls were Caucasian. Genotype II was identified in 15 patients with COPD, genotype ID in 31 and genotype DD in 20. In the control group, genotype II was identified in 19 persons, genotype ID in 68 and genotype DD in 31. The distribution of ACE gene polymorphism did not differ between patients and the control group. RESULTS: In patients with COPD, no differences were seen between the three genotype groups in mean age, smoking history, hemoglobin concentrations or ventilometric or blood gas variables. Both systolic and mean Ppa differed significantly between the II, ID and DD groups (Systolic Ppa: 24.4 +/- 2.2 versus 31.3 +/- 2.5 and 36.7 +/- 3.9 mm Hg, respectively, ANOVA, p < 0.05; Mean Ppa: 13.0 +/- 1.5 versus 17.5 +/- 1.4 and 21.2 +/- 2.8 mm Hg, respectively, ANOVA, p < 0.05). In multiple linear regression analysis, the I/D ACE gene polymorphism (p < 0.05), SaO2 (p < 0.05) and the duration of COPD (p < 0.02) were independent predictors of systolic and mean Ppa. CONCLUSION: The results of the study suggest that I/D ACE gene polymorphism is linked to pulmonary artery pressure in Caucasian patients with COPD.     

Increased deformability of red blood cells is associated with a deletion polymorphism of the angiotensin-converting enzyme gene

Angiotensin-converting enzyme (ACE) plays important roles in the renin-angiotensin system. ACE converts angiotensin I to angiotensin II and also inactivates bradykinin, thereby modulating the vascular tone. A polymorphism of the ACE gene, located on chromosome 17, has been found in intron 16, and is characterized by the presence (insertion [I]) or absence (deletion [D]) of a 287-base-pair Alu repeat. Individuals with the D allele of the ACE gene have higher ACE levels and are at higher risk of cardiovascular events. We aimed to investigate the possible relationship between the I/D polymorphism of the ACE gene and hemorheological parameters, including red blood cell (RBC) deformability. The study was performed on 28 healthy young volunteers (13 women and 15 men, mean age 24 +/- 2). The prevalence of the I and D alleles was 30.4% and 69.6%, respectively. The I/I genotype (II) was found in 21.4%, I/D genotype (ID) in 17.9%, and D/D genotype (DD) in 60.7% of the subjects tested. No significant relationship between ACE I/D polymorphism and RBC aggregation or whole blood and plasma viscosity was observed. In contrast, RBC deformability was significantly increased in the subjects with the DD genotype compared with the II (p < 0.05) or the ID (p < 0.01) genotype, and in the subjects with the D allele compared with the I allele (p < 0.01). We suggest that RBC deformability of individuals with the D allele, who have higher risk for cardiovascular pathologies, may have been increased by a compensatory mechanism.     

肾素-血管紧张素系统基因多态性与冠状动脉血栓疾病

为了观察中国人群中肾素-血管紧张素系统基因多态性的分布特征，并分析这些基因多态性与冠状动脉血栓(CATD)疾病的相关性以及该基因多态性间的相互作用，采用直接聚合酶链式反应(PCR)和PCR-限制性片段长度多态性(PCR—RFLP)方法对192例冠状动脉血栓疾病患者和110例对照组个体进行血管紧张素转换酶(ACE)、血管紧张素原(AGT)和血管紧张素II I型受体(AT1R)基因的基因多态性进行检测。结果表明：①在中国人群中，ACE基因各基因型分布分别为DD12．2％、ID43．9％和II43．9％；AGT基因各基因型分布为MM8．2％，MT36．7％和TT55．1％；AT1R基因各基因型分布分别为AA91．8％和AC8．2％。②冠状动脉血栓疾病组与对照组相比，上述3种基因多态性的分布均无明显差异。③同时携带AT1R—AC和AGT—TT基因型的个体，与AT1R—AA和AGT—TT基因型个体相比，罹患CATD的相对危险度达到3．517(95％C10．988—12．527)；与AC基因型和非TT基因型个体相比，罹患CATD的危险性可增加至15．000(95％CI 1．940—115．963)；在AT1R—AC基因型个体，等位基因D在CATD组和对照组的分布亦存在有明显的差异(P=0．017)。结论：我国人群ACE基因I／D多态性、AGT基因M235T多态性和ATlR基因A1166C多态性各基因型和等位基因的分布明显不同于西方人群；上述3种基因多态性不是我国人群冠状动脉血栓疾病或心肌梗塞的独立的危险因素。但AT1R基因AC基因型与AGT基因TT基因型、AT1R基因AC基因型和ACE基因等位基因D在罹患冠状动脉血栓疾病的危险性上有显著的协同作用。     

Angiotensin converting enzyme gene polymorphism and glomerular filtration rate changes in type 2 diabetic patients

It has been suggested that an insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene may be associated with diabetic nephropathy The aim of this study was to investigate whether an association exists between ACE I/D polymorphism and glomerular filtration rate (GFR) in type 2 diabetes mellitus. A total of 128 type 2 diabetic patients were included in the study with the following ACE genotype distribution: DD 40, ID 58,11 30. I/D polymorphism was determined by polymerase chain reaction (PCR). Mean GFR was not statistically different according to ACE genotype (DD: 89.9 +/- 28.1 ml/min, ID: 99.5 +/- 25.1 ml/min, II: 96.6 +/- 19.6 ml/min). There was no significant difference in genotype distribution in normo-, micro- and macroalbuminuric patients (DD:ID:II [%], normo- 35:46:19, micro-28:55:17, macro- 31:55:14). ACE I/D polymorphism does not seem to be associated with GFR in type 2 diabetic patients.