冠心病与血管紧张素转换酶和内皮型一氧化氮合酶基因多态性及交互作用的临床研究

目的联合对冠心病患者血管紧张素转换酶（ACE）基因多态性和内皮型一氧化氮合酶（eNOS）基因G894T多态性进行分析,探讨基因多态性与冠心病的关系和交互作用及遗传学机制在冠心病发病及预后中的临床意义。方法应用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）分析技术检测236例冠心病患者及190例正常人ACE和eNOS两种基因多态性。同时测定血脂、血糖、体重指数（BMI）、左室射血分数（LVEF）和血压。结果冠心病组ACE基因DD型频率[36％（86／236）]显著高于对照组[19％（36／190）,P〈0．01],Ⅱ型频率[27％（64／236）]显著低于对照组[49％（93／190）,P〈0．05]。冠心病组DD型甘油三酯（TG）[（2．2±1．7）mmol／L]显著高于Ⅱ型TG[（1．6±0．8）mmol／L和ID型TG[（1．7±0．9）mmol／L,均P〈0．05],DD型高密度脂蛋白胆固醇[HDL—C（1．2±0．4）mmol／L]显著低于Ⅱ型HDL—C[（1．3±0．3）mmol／L,P〈0．05],DD型血糖[（6．2±1．7）mmol／L]和BMI[（25．7±2．8）kg／m^2]显著高于ID型[血糖：（5．6±1．3）mmol／L,BMI：（24．8±3．1）kg／m^2。,P〈0．05],DD型LVEF（56％±14％）显著低于Ⅱ型LVEF（62％±15％）和ID型LVEF（61％±14％）,均P〈0．05。收缩压、舒张压、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、糖尿病组与非糖尿病组、急性冠状动脉综合征组与非急性冠状动脉综合征组、单支病变组与多支病变组在ACE和eNOS基因不同基因型之间差异均无统计学意义。冠心病组eNOS基因GT型频率[28％（67／236）]显著高于对照组[17％（32／190）,P〈0．01],GG型频率与对照组比较,差异无统计学意义。TG、HDL—C、血糖、BMI和LVEF在eNOS基因不同基因型之间差异均无统计学意义（均P〉0．05）。携带DD型患冠心病的概率是携带Ⅱ型的1．74倍（P〈0．01）,携带GT型患冠心病的概率是携带GG型的1．73倍（P〈0．05）。两种基因对患冠心病的交互作用显示为如同时携带Ⅱ型和GG型,患冠心病的概率是37．9％,而同时携带DD型和GT型患冠心病的概率是77．8％。结论ACE基因多态性和eNOS基因多态性与冠心病及某些危险因素显著相关,同时携带DD型和GT型两种易患基因型时,患冠心病的概率明显增加,具有显著的遗传倾向。     

血管紧张素转换酶基因多态性对冠心病患者血管内皮舒张功能的影响

目的:观察血管紧张素转换酶(ACE)基因多态性对冠心病患者内皮功能的影响及其抑制剂的干预作用.方法:选取冠心病患者(冠心病组)68例,对照组69例,聚合酶链反应(PCR)检测ACE基因插入/缺失(L/D)多态性,超声检测肱动脉内皮功能.结果:冠心病组DD基因型明显高于对照组.冠心病组ACE各基因型内皮依赖性舒张功能均低于对照组,DD基因型最为明显;非内皮依赖性舒张功能差异无显著性.血管紧张素转换酶抑制剂(ACEI)治疗后冠心病组各型肱动脉内皮依赖性舒张功能与治疗前比较均有显著性改善,其中DD基因型改善最为明显.结论:冠心病患者血管内皮功能异常与ACE基因I/D多态性相关.ACEI可以改善内皮功能,特别是对DD基因型患者改善更为明显.     

The DD genotype of angiotensin converting enzyme polymorphism is a risk factor for coronary artery disease and coronary stent restenosis in Japanese patients

Stent implantation has decreased the incidence of restenosis after coronary intervention, but has not eliminated it. The contribution of the angiotensin-converting enzyme (ACE) genotype to the development of coronary artery disease and restenosis after coronary stenting was investigated in 67 Japanese patients in whom 103 lesions in which stents had been successfully implanted were assessed by quantitative coronary angiography, before, immediately after coronary stenting, and during follow-up. The distribution of the patients with the DD, ID, and II genotypes was 13%, 54%, and 33%, respectively. The prevalence of multivessel disease in the DD genotype was significantly higher (DD genotype: 78%; ID genotype: 58%; II genotype: 27%, chi2=8.13, p=0.016) and the late loss in the DD genotype (1.43+/-0.96 mm) was significantly greater (ID genotype: 0.78+/-0.98 mm and II genotype: 0.79+/-0.88 mm, p<0.05 vs DD genotype). However, there was no significant difference in the restenosis rate among the 3 genotypes. The present study in Japanese patients indicates that the DD genotype is associated with more extensive coronary artery disease and progression of the inward remodeling within the stented lesion, which is primarily caused by neointimal hyperplasia.     

血管紧张素转换酶基因多态性与非杓型高血压的关系

目的研究血管紧张素转换酶 ( ACE)基因插入 /缺失 ( I/ D)多态性与非杓型高血压 ( EH)的关系。方法　 1应用聚合酶链反应 ( PCR)方法扩增 5 0例正常人、99例高血压患者的 ACE基因上 2 87bp片段 ,根据插入 ( I)或 /缺失( D)来判断其多态性。 2高血压患者行 2 4h动态血压监测 ( ABPM) ,根据 ABPM结果分为杓型 EH组和非杓型 EH组。结果　 1非杓型组与健康对照组相比 ,其 D等位基因及 DD基因型显著升高。 2非杓型组与杓型组相比 ,其 D等位基因及 DD基因型显著升高。3杓型组与健康对照组相比 ,ACE基因型和等位基因频率无显著性差异。结论　ACE基因多态性与非杓型高血压有关联性 ,DD基因型提示可能与高血压昼夜节律改变有关     

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.     

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study.

Objectives: We investigated the association between insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene, the presence and extent of coronary artery disease, and myocardial infarction. Background: The D allele of the ACE gene has been associated with coronary artery disease and myocardial infarction, but this association has been challenged in epidemiological studies. Methods: Nine hundred and sixty-nine men and 341 women undergoing coronary angiography were studied. The ACE genotypes were assessed by polymerase chain reaction from genomic deoxyribonucleic acid, homozygosity for the D allele was controlled using an insertion-specific primer. Coronary artery disease was defined by angiographic criteria, the extent of coronary artery disease by the number of coronary arteries with >/=50% lumen narrowing. Results: The ACE genotypes did not differ in terms of age, sex, body mass index, blood pressure, plasma lipids or lipoproteins. We found no association between the ACE genotypes and coronary artery disease (odds ratio, 95% confidence interval in DD genotypes for coronary artery disease in men 0.97, 0.70-1.36; in women 1.56, 0.95-2.57), extent of coronary artery disease (men 1.17, 0.85-1.61; women 1.24, 0.65-2.34), or myocardial infarction among the patients with coronary artery disease (men 1.07, 0.78-1.48; women 0.95, 0.50-1.76). The ACE genotype was not associated with coronary artery disease or myocardial infarction in hypertensives (n=771; odds ratio for coronary artery disease 0.93, 0.65-1.34; odds ratio for myocardial infarction 0.94, 0.66-1.33), or in patients 相似文献   

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.     

Genotype combinations of plasminogen activator inhibitor-1 and angiotensin-converting enzyme genes and risk for early onset of coronary heart disease.

BACKGROUND: Both angiotensin-converting enzyme genotype and plasminogen activator inhibitor type 1 genotype have an effect on fibrinolytic components and hence, may increase risk or advance occurrence of coronary heart disease. We examined the association of the angiotensin-converting enzyme and the plasminogen activator inhibitor type 1 genotypes, and their combinations, with early onset of coronary heart disease in a cohort of 907 patients with coronary heart disease. DESIGN AND METHODS: All patients with a coronary heart disease (International Classification of Diseases, 9th Rev. pos. 410-414), aged 30-70 years and participating in an inpatient rehabilitation program between January 1999 and May 2000 in two clinical centres in Germany were enrolled. The plasminogen activator inhibitor type 1 and the angiotensin-converting enzyme genotypes were determined by polymerase chain reaction, and the distribution was compared between patients with early (< or =55 years) and late (>55 years) onset of coronary heart disease. A multivariate analysis was employed to adjust for potentially confounding factors. RESULTS: Of the 907 included patients, 408 (45.0%) developed coronary heart disease before the age of 55 years. For the 4G/4G genotype of plasminogen activator inhibitor type 1 the odds ratio for early onset of coronary heart disease was 1.68 [95% confidence interval (CI) 1.01-2.57] and for the D/D genotype of angiotensin-converting enzyme the odds ratio was 1.22 (95% CI 0.84-1.76) after adjustment for covariates. In multivariate analysis an odds ratio of 3.10 (95% CI 1.51-6.36) was found for the association between the combined homozygosity for both polymorphisms (plasminogen activator inhibitor type 1 genotype 4G/4G and angiotensin-converting enzyme genotype D/D) and onset of coronary heart disease before the age of 55 years after controlling for sex, age, smoking, diabetes, hypertension, hyperlipidemia and school education. CONCLUSION: The co-existence of the 4G/5G polymorphism of the plasminogen activator inhibitor type 1 gene and the I/D polymorphism of the angiotensin-converting enzyme gene increases the risk for early onset of coronary heart disease in this population.     

急性冠状动脉综合征患者血管紧张素转换酶基因插入/缺失多态性分析

目的 以急性冠脉综合征(ACS)患者为研究对象,探讨ACE基因插入/缺失(I/D)多态性在其发病中的作用.方法 利用多聚酶反应(PCR)方法对169例急性冠脉综合征(ACS)患者及94例正常健康人的血管紧张素转换酶(ACE)基因插入/缺失多态性变异进行对比分析.结果 ACS患者ACE基因DD型及D等位基因频率明显高于对照组(DD,0.385:0.213;D,0.583:0.441),而且ACE基因各型间其它冠心病危险因素比较无统计学差异.结论在国人中ACE基因DD型可能是ACS发病的独立因素.     

Renin-angiotensin system polymorphisms and coronary artery surgery patients

The frequencies of angiotensin-converting enzyme gene insertion/deletion, angiotensinogen-M253T, and angiotensin II type 1 receptor-A1166C polymorphisms were analyzed in 105 patients undergoing coronary artery bypass grafting (group 1) and a control group of 105 non-cardiac patients (group 2). Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by polymerase-chain-reaction-based restriction analysis. According to the angiotensin-converting enzyme gene insertion/deletion polymorphism, 36.3% of patients in group 1 and 30.7% in group 2 were homozygous for the DD allele. This difference was not statistically significant. Angiotensin II type 1 receptor-A1166C genotype polymorphism was also not significantly different between the groups. The results showed the angiotensinogen-M235T polymorphism to be heterogenous. The MM homozygote frequency was significantly higher in controls (72.3%), whereas 80% of the TT homozygote frequency was in the surgical group ( p = 0.001). These results show that although there were no significant differences in angiotensin-converting enzyme gene insertion/deletion and angiotensin II type 1 receptor-A1166C genotype polymorphisms between the groups, angiotensinogen-M235T polymorphism of TT homozygote frequency was significantly associated with patients undergoing coronary artery bypass surgery.     

Progression of atherosclerosis in patients with peripheral arterial disease as a function of angiotensin-converting enzyme gene insertion/deletion polymorphism

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism plays a role in determining the inter-individual variability of circulating angiotensin-converting enzyme activity and intracellular angiotensin-converting enzyme levels. Angiotensin-converting enzyme, as a key enzyme in the renin-angiotensin system, catalyzes the activation of the vasoconstricting and proliferation-stimulating angiotensin II and breaks down the vasodilatory peptide bradykinin. It is assumed that the excess supply of angiotensin II (due to the deletion polymorphism of the angiotensin-converting enzyme gene) contributes to endothelial dysfunction and in this way promotes the onset and progression of atherosclerosis. The aim of this study was to test whether the presence of the deletion allele of the angiotensin-converting enzyme gene predisposes a more rapid systemic progression of a preexisting peripheral arterial disease. To this end, the course of disease was surveyed for an average of 5 years in 97 patients who were angiotensin-converting enzyme gene-typed and suffered from a stable stage II peripheral arterial disease according to Fontaine. These patients did not suffer from an additional coronary artery disease, a cerebrovascular disease, or other serious illness. A local progression in the periphery or a systemic progression in the coronary or cerebrovascular areas was regarded as study endpoints. Of the patients, 49.5% showed an atherosclerosis progression during the surveillance period. With II-carriers, a progression was registered in 42.1% and with DD carriers, progression was seen in 59.4%. D/I allele frequencies were seen in patients with progression at a level of 0.60/0.40 vs 0.55/0.45 for patients without progression. The average duration of disease in stable stage II (before progression appeared) amounted to 108 +/- 14 months for II carriers, 88 +/- 8 months for ID carriers, and 92 +/- 11 months for DD carriers (p = 0.21). Based on these findings, the deletion polymorphism of the angiotensin-converting enzyme gene is not an independent risk factor for progression of atherosclerosis in patients with peripheral arterial disease.     

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and vasospastic angina

Background and hypothesis: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary atherosclerosis and myocardial infarction, but its relation to vasospastic angina has not been fully proven. In the present study, we investigated the possible relationship between the ACE I/D genotype and vasospastic angina. Methods: We explored the distribution of the ACE genotype in 20 patients with vasospastic angina without fixed coronary artery stenosis, 55 angina patients with fixed coronary artery stenosis, and 30 control subjects without coronary artery disease. Results: The frequency of the DD genotype in patients with vasospastic angina (DD: 30.0%, ID: 20.0%, II: 50.0%) did not differ from that in the control subjects (DD: 23.3%, ID: 26.7%, II: 50.0%), while the frequency in patients with coronary artery stenosis (DD: 43.7%, ID: 21.8%, II: 34.5%) was significantly higher than that in the control subjects. The frequency of the D allele also did not differ between patients with vasospastic angina (0.40) and control subjects (0.37), while the frequency was significantly higher in patients with coronary artery stenosis (0.55). Conclusions: These findings suggest that the ACE DD genotype is a potent genetic risk factor for organic coronary artery disease, while it confers no appreciable increase in risk of vasospastic angina. These results also suggest the diversity of the pathogenesis of vascular lesions in these two types of coronary artery disease.     

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.     

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease

OBJECTIVE: To analyse the relation between overweight, obesity and fat distribution with I/D polymorphism of the angiotensin-converting enzyme (ACE) gene and its association with coronary heart disease (CHD). DESIGN: Cross-sectional, case-control study. SUBJECTS: A total of 185 cases (141 males) who had suffered at least one episode of CHD and 182 controls (127 males). MEASUREMENTS: Body mass index, waist circumference, blood pressure, plasma total cholesterol, triglycerides, HDL cholesterol and fasting glucose were measured with standard methods, genotyping the I/D polymorphism of ACE gene. RESULTS: Obesity and abdominal fat deposit are associated with CHD in women, but not independently. We have found an association between obesity and abdominal fat deposit with the ACE gene I/D polymorphism in subjects with CHD. Subjects with CHD and DD or ID genotypes have significantly higher prevalence of obesity and abdominal fat deposit and higher values of weight and waist circumference. In addition, the DD and ID genotypes increased crude OR of obesity. The DD and ID genotypes of the ACE gene I/D polymorphism and BMI are independently associated with CHD. CONCLUSION: There is a relation between the type and grade of obesity with the genotypes of the ACE gene I/D polymorphism in subjects with CHD.     

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。     

Angiotensin-converting enzyme gene I/D polymorphism and carotid artery disease in renovascular hypertension

There is evidence linking the activation of the renin-angiotensin system (RAS) with target organ damage in renovascular hypertension (RVH). A genetic association of the DD genotype of the angiotensin-converting enzyme (ACE) gene with cardiovascular complications has been found in various clinical conditions. The aim of our study was to determine whether the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the high prevalence of target organ damage reported in RVH. A total of 65 atherosclerotic patients (age 68.2 +/- 5.2 years) with RVH and 49 atherosclerotic patients (age 68.0 +/- 6.3 years) with essential hypertension (EH) were sequentially enrolled when attending the outpatient clinic for specialist assessment of their vascular disorder. Cardiac, renal, and vascular involvement were assessed in both groups and blood was taken for genetic analysis. Patients with RVH had a higher prevalence of left ventricular hypertrophy (LVH), carotid artery disease, and albuminuria than those with EH. In RVH, but not in EH, the DD genotype was significantly associated with severe arterial disease. In RVH, carotid disease (lumen narrowing >60%) was present in 62% of DD patients versus 25% of the other genotypes (OR = 4.90, 95% CI: 1.70-14.13). Such an association was also present in peripheral vascular disease: 72.4% in DD patients versus 41.6% in the other genotypes (OR = 3.67, 95% CI = 1.29-10.36). Logistic regression analysis showed that the DD genotype was the strongest predictor of risk of severe carotid disease. We conclude that, in atherosclerotic RVH, there is an association of the severity of vascular disease with the DD genotype of the ACE gene.     

Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with pulmonary hypertension in patients with COPD

In this cross-sectional controlled study, we aimed to investigate the role of polymorphisms of the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes on pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD). Forty-two (41 male, 1 female, mean age: 62 +/- 7 years) COPD patients and 40 (all male, mean age: 60 +/- 8 years) healthy controls were included. Respiratory function tests, arterial blood gases, and echocardiographic examinations were performed. ACE and eNOS genotypes were determined using PCR. The ACE and eNOS genotype distribution was not significantly different between COPD patients and controls. On comparing pulmonary artery pressures in different eNOS genotypes, the mean pulmonary artery pressure (Ppa) in patients with the BB genotype was significantly higher than in patients with the nonBB genotypes (41.3 +/- 17.7 mmHg vs. 27.3 +/- 11.2 mmHg, P = 0.02). However, there was no difference in ACE genotype distributions between COPD patients with and without pulmonary hypertension. In stepwise linear regression analysis for predicting pulmonary artery pressure, PaO2 and polymorphism of eNOS gene were found to be independent variables. In conclusion, BB-type polymorphism of the eNOS gene has been associated with PH in addition to hypoxemia. However, ACE gene polymorphism was not found to be associated with PH.     

Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors

OBJECTIVES: This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis. BACKGROUND: In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this. METHODS: Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed. RESULTS: At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006). CONCLUSIONS: The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.     

Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND: Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION: Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.     

Association of genetic polymorphisms in the ace,apoe, and tgfβ genes with early onset ischemic heart disease

Background: The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD. Hypothesis: This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor β2 (TGF β2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD. Methods: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF β2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories. Results and Conclusion: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF (32 gene was rare and not associated with early onset IHD.