血管紧张素转化酶基因多态性与老年高血压及合并糖尿病的相关性研究

目的 探讨血管紧张素转化酶(ACE)基因插入/缺失(I/D)多态性与老年人原发性高血压及合并糖尿病患者的关系.方法 应用聚合酶链反应(PCR)技术对60名正常对照组,105例老年高血压患者,38例老年高血压合并糖尿病患者进行ACE基因I/D多态性检测.结果 老年高血压患者中的DD基因型频率(0.352)和等位基因频率(0.543),老年高血压合并糖尿病患者的DD基因型频率(0.421)和等位基因频率(0.579)均明显高于正常对照组的0.133和0.250,而老年高血压组与老年高血压合并糖尿病组患者的DD基因型频率和D等位基因频率之间的差别无显著性.结论 ACE基因缺失型是老年高血压的危险因素,但ACE基因缺失不是糖尿病的危险因素之一.     

ACE基因多态性与PTCA合并支架植入术后再狭窄的相关性研究

目的:探讨血管紧张素Ⅱ转换酶(ACE)基因的多态性与PTCA合并支架植入术后发生支架内再狭窄(ISR)的相关性。方法:选取2001-2003年入我院治疗,成功实施PTCA合并支架植入手术的华东地区冠心病患者共197例,并作为期半年的追踪随访,按照二次冠状动脉造影结果分为术后再狭窄组和未狭窄组,然后运用PCR技术对这197例患者样本进行ACE基因分型,最后采用统计学方法判断ACE基因多态性是否与支架内再狭窄具有相关性。结果:197例患者中再狭窄组为58例,ACE基因型DD、DⅠ、Ⅱ的频率分别为25.9%、39.6%、34.5%;未狭窄组为139例,ACE基因型DD、DⅠ、Ⅱ的频率分别为33.8%、43.9%、22.3%,两组间无显著差异(x2=3.2N).P>0.05)。再狭窄组和未狭窄组的D等位基因的频率分别为52.6%和55.8%,亦无显著差异(x2=3.326.P>0.05)。结论:ACE基因1/D多态性与支架术后再狭窄无相关性。     

糖尿病视网膜病变与载脂蛋白E基因多态性的关系

目的 :研究载脂蛋白 E基因多态性与糖尿病视网膜病变的关系。方法 :选择 14 5例 2型糖尿病患者 (合并或不合并有糖尿病视网膜病变 )及年龄、性别相匹配的 90例正常对照组 ,聚合酶链反应 -限制性片段长度多态性 (PCR-RFL P)方法检测 Apo E基因型。比较各组基因型及等位基因频率分布。结果 :对照组、糖尿病视网膜病变组及糖尿病非视网膜病变组 3组 Apo E基因型及等位基因频率均无显著差异。结论 :Apo E基因多态性与糖尿病发病无关 ,并且与是否并发视网膜病变无关     

妊娠高血压综合征患者血管紧张素转换酶基因多态性研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失多态性与妊娠高血压综合征(PIH)的关系。方法应用聚合酶链反应(PCR)检测92例PIH患者及85名正常妊娠者的ACE基因多态性。结果PIH组ACE基因3种基因型频率分别为DD型44.6%、ID型33.7%、Ⅱ型21.7%,对照组ACE基因3种基因型频率分别为DD型18.8%、ID型40.0%、Ⅱ型41.2%;两组的DD基因型及D等位基因频率比较差异有显著性(P<0.05)。结论ACE基因的缺失多态性(DD)可能为妊高征发病的重要遗传因素之一。     

冠心病患者冠脉病变严重程度与血管紧张素转换酶基因多态性的相关性研究

目的 :研究血管紧张素转换酶 (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 :采用聚合酶链式反应 (PCR )技术检测 12 2例冠心病患者和 80例健康人群ACE基因多态性 ,并对病例组进行冠状动脉造影 ,判定冠脉病变支数和危险记分。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基因型和D等位基因频率显著高于对照组 (P <0 0 5 )。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 0 5 )。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。     

高血压合并脑梗死发病的危险因素:血管紧张素转换酶基因的多态性与血清血管紧张素转换酶水平的关系

目的:研究高血压合并脑梗死患者血管紧张素转换酶(angiotensincon-vertingenzyme,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。方法:应用聚合酶链反应(PCR)方法测定了白求恩国际和平医院54例高血压合并脑梗死患者(排除冠心病及各类心肌病),40例高血压但无心脑血管并发症患者(排除继发性高血压)和54例门诊体检健康者的ACE基因I/D多态性,并采用紫外分光光度测定法测定其血清ACE水平。结果:高血压合并脑梗死患者ACED等位基因频率(66.7%)显著高于高血压组(52.5%)及对照组(49.1%),差异有显著性或非常显著性意义(P<0.05或0.01),且DD型基因者具有较高的血清ACE水平。结论:ACE基因I/D多态性与血清ACE水平密切相关,ACED等位基因可能为高血压合并脑梗死的独立危险因素。     

血管紧张素转换酶基因与中国人群冠心病、高血压病及糖尿病的关系

目的：研究血管紧张素转换酶(ACE)基因与中国人群冠心病(CHD)、高血压病(EH)及2型糖尿病(T2DM)的关系。方法：250例呈不同组合的EH、T2DM以及CHD患者及90例正常对照用改良的聚合酶链反应(PCR)方法检测ACE基因型，比较基因型及等位基因频率分布。结果：①无合并CHD的T2DM及EH组ACE基因型及等位基因频率与正常对照无显著差异；②CHD组无论是否合并EH及／或T2DM，Ⅲ基因型及Ⅰ等位基因频率均显著低于正常对照，而DD基因型及D等位基因频率均显著高于正常对照；③T2DM合并CHD组及EH合并CHD组中Ⅱ基因型及Ⅰ等位基因频率均显著低于正常对照，而DD基因型及D等位基因频率均显著高于正常对照。结论：ACE基因多态性与中国人群CHD相关。这种关联亦见于EH或T2DM合并CHD中，但ACE基因仅是CHD发病的遗传学基础，而与是否合并EH及／或T2DM无关。     

血管紧张素转化酶及血管紧张素Ⅱ-1型受体基因多态性与高血压相关性

目的 探讨血管紧张素转化酶(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A1166C多态性与原发性高血压(EH)的相关性,以及多种危险因素与EH的关系.方法 选取125例健康者(对照组)和148例EH患者(EH组)作为研究对象作问卷调查、医学体检和血液生化项目检测,应用聚合酶链反应(PCR)技术检测研究对象ACE基因的I/D多态性;应用PCR、限制性内切酶酶切的方法检测AT1R基因A1166C多态性,并用Logistic回归筛选高血压的危险因素.结果 EH组和对照组的DD基因型频率和D等位基因频率差异均不显著.EH组的AC基因型频率23.0%,C等位基因频率11.5%,均显著高于对照组的12.8%和6.4%.EH组ACE基因DD型+AT1R基因AC型联合基因型频率7.4%,显著高于对照组的1.6%.多因素Logistic回归结果表明,EH的危险因素主要有BMI、EH家族史和DD+AC联合基因型.结论 ACE基因D等位基因可能与EH发病无关联;AT1R基因A1166C多态性可能是EH的重要遗传因素;DD+AC联合基因型对EH的发病有显著的联合促进作用.     

血管紧张素转换酶及血管紧张素原基因多态性与高血压左室肥厚的相关研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性及血管紧张素原(AGT)基因M235T多态性与高血压左室肥厚(LVH)的关系。方法对68例超声心动图诊断的未接受治疗的高血压合并LVH患者与76例高血压非LVH患者进行病例对照研究。采用聚合酶链式反应(PCR)与限制性片段长度多态性(RFLP)技术检测ACE基因I/D多态性及AGT基因M235T变异。以二维引导的M型超声心动图测量并计算左室重量。结果①该组高血压患者ACE与AGT基因型的分布均符合Hardy Weinberg平衡。②ACE基因I/D基因型在LVH组与非LVH组的分布差异有显著性(χ2=6.777,P<0.05)。LVH组DD基因型与D等位基因的频率均高于非LVH组(DD基因型:0.31vs0.13,χ2=6.674,P=0.01;D等位基因:0.54vs0.41,χ2=4.837,P<0.05)。③AGT基因M235T基因型在LVH组与非LVH组的分布差异有显著性(χ2=7.133,P<0.05)。LVH组TT基因型与T235等位基因的频率均高于非LVH组(TT基因型:0.62vs0.40,χ2=7.133,P<0.01;T235等位基因:0.78vs0.65,χ2=5.741,P<0.05)。④联合基因分析显示,LVH组ACE DD+AGT TT基因型频率显著高于非LVH组(0.22vs0.05,χ2=8.839,P<0.01),具有该联合基因型者发生LVH的风险比数比(OR=5.094)明显高于单独具有ACE DD基因型(OR=2.949)或AGT TT基因型(OR=2.477)者。结论ACE     

糖尿病视网膜病变患者ApoE等位基因多态性的研究

目的探讨糖尿病视网膜病变患者及糖尿病未伴发视网膜病变患者ApoE等位基因多态性及其之间的关系。方法糖尿病患者根据是否伴发眼底病变分为两组:糖尿病视网膜病变组(DR组)和糖尿病未伴发视网膜病变组(NDR组)。应用PCR-荧光探针法分别检测两组患者的ApoE基因型并对结果进行统计学分析。结果 ApoE基因型在DR组和NDR组间差异无统计学意义(P0.05),DR组ApoE等位基因频率ε2明显高于NDR组(P0.05)。结论 ApoE基因型与糖尿病患者是否并发视网膜病变无关,ApoE等位基因ε2可能是糖尿病伴发视网膜病变的危险因素。     

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 polymorphism and proliferative retinopathy in type 1 diabetes: results of a case-control study.

OBJECTIVE: To evaluate the relationship between the ACE insertion/deletion polymorphism and proliferative diabetic retinopathy in patients with type 1 diabetes of long duration. Based on epidemiological and pathophysiological findings, risk factors apart from glycemic control and duration of disease are likely to be involved in the development of proliferative retinopathy. RESEARCH DESIGN AND METHODS: In this case-control study, we compared 81 patients with longstanding (> or =20 years) type 1 diabetes who had nonproliferative (mild or moderate background) retinopathy with 95 patients with diabetes of similar duration and HbA1c who had proliferative retinopathy. To avoid the confounding effect of nephropathy, patients with overt nephropathy were excluded, and microalbuminuria was introduced into the multiple logistical regression model. The polymorphic region in intron 16 of the ACE gene (17q23) was analyzed using the polymerase chain reaction. RESULTS: The ACE genotype distribution in patients with proliferative retinopathy (DD 39.4%, ID 48.9%, II 11.7%) was significantly different (P < 0.001) from that of patients with nonproliferative retinopathy (DD 17.3%, ID 54.3%, II 28.4%). In a multiple logistical regression analysis, the adjusted relative risk for proliferative retinopathy in a patient with a DD genotype compared with a patient with an II genotype was 6.6 (95% CI 2.2-19.5), P = 0.0026. In addition to genotype, systolic blood pressure (odds ratio 1.027 [95% CI 1.0-1.1], P = 0.0093) but not microalbuminuria (< or =20 vs. > or =20 microg/min) reached statistical significance in the multiple regression model. Because subjects were matched regarding diabetes duration and HbA1c, we did not interpret the respective parameter estimates. CONCLUSIONS: These data provide evidence that deletion in the ACE gene is associated with the prevalence of proliferative retinopathy in type 1 diabetes and suggest that the DD genotype confers susceptibility to proliferative retinopathy independent of diabetic nephropathy     

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.     

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.     

Prognostic effect of insertion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes

OBJECTIVE: The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 +/- 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine >/=500 micromol/l, or doubling of plasma creatinine of baseline value >/=150 micromol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis. RESULTS: The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49-5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points. CONCLUSIONS: The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 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.     

Angiotensin-converting enzyme insertion/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuria

Angiotensin-converting enzyme (ACE) gene polymorphism is thought to be a potent risk factor for nephropathy and retinopathy in diabetes. We investigated the association between polyneuropathy and gene polymorphisms of both the ACE insertion/deletion (I/D) and angiotensinogen (AGT) M235T genes in 84 type 2 diabetic patients without macroalbuminuria (21 with polyneuropathy and 63 without). ACE genotype distribution did not differ significantly between patients with and without polyneuropathy, but the frequency of the I allele was significantly higher in those with polyneuropathy than in those without. In contrast, neither the genotype distribution nor the allele frequencies of the AGT gene differed between the two groups. In logistic regression analysis using a D-additive model, the D allele had a protective effect on polyneuropathy (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.88). A D-dominant model hypothesis also gave a significant OR (0.28; 95% CI, 0.09-0.90). ACE I/D polymorphism, but not AGT M235T polymorphism, may affect polyneuropathy development in type 2 diabetes without macroalbuminuria.     

血管紧张素转换酶基因多态性及血清水平与脑梗死的关系

目的研究血管紧张素转换酶（ACE）基因多态性及血清ACE水平与脑梗死之间的相互关系及可能机制。方法对84例脑梗死患者和74例健康对照者用聚合酶链反应（PCR）技术和琼脂糖凝胶电泳法分别进行ACE基因插入／缺失（I／D）多态性测定。分析比较脑梗死组与健康对照组之间ACE基因多态性的分布差异。结果脑梗死组DD基因型频率（50％）和D等位基因频率（64％）与健康对照组（分别为28％、4600）比较增高,差异有统计学意义（分别为P〈0．01,P〈0．05）。ACE基因多态性与血清ACE水平有关,ACE水平依次为：DD型〉ID型〉Ⅱ型,三者相互之间差异有统计学意义（P〈0．01）。结论ACE基因多态性与血清ACE水平和脑梗死有关,其DD型基因和D等位基因是脑梗死的危险因素。