Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.     

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   

Mild renal insufficiency is associated with angiographic coronary artery disease in women

BACKGROUND: Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results- Women with chest pain who were referred for coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (r=0.11, P<0.004) and maximum coronary artery stenosis (r=0.11, P<0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (>/=50% diameter stenosis in >/=1 coronary artery) (61% versus 37%; P<0.001) and CAD in multiple vessels (P<0.001 for association) and had greater maximum percent diameter coronary stenosis (59+/-35% versus 38+/-36%; P<0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2). CONCLUSIONS: In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.     

Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated With Coronary Artery Plaque Calcification As Assessed by Intravascular Ultrasound

Objectives. We evaluated the influence of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque morphology and calcification in patients with angiographically documented coronary artery disease (CAD).Background. The ACE I/D polymorphism has been associated with an increased risk of myocardial infarction in patients with the DD genotype but not with the presence of native CAD.Methods. We studied 146 patients undergoing percutaneous transluminal coronary angioplasty for stable angina pectoris by means of preinterventional intravascular ultrasound (IVUS). Qualitative and quantitative criteria were used to classify the target lesions as poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion-specific PCR in DD genotypes to prevent mistyping.Results. The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the basic characteristics. Patients with the DD genotype had significantly more calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95% confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180° of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05 to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31).Conclusions. Patients with CAD and the ACE DD genotype have a significantly higher incidence and greater extent of coronary lesion calcification, as determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is related to the development or progression of atherosclerotic plaque calcification.     

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.     

Angiotensin I-converting enzyme (ACE) inhibitors and restenosis after coronary artery stenting in patients with the DD genotype of the ACE gene

OBJECTIVES: We tested the hypothesis that patients with the DD genotype of the angiotensin I-converting enzyme (ACE) gene who are treated with ACE inhibitors are at a higher risk of restenosis after coronary stent placement than patients who do not receive ACE inhibitors. BACKGROUND: Two recent studies with a limited series of patients carrying the DD genotype suggested an unfavorable impact of the use of ACE inhibitors on the restenotic process after implantation of stents in coronary arteries. Because these findings may question the use of ACE inhibitors after coronary stenting, we examined this important issue in a large series of patients. METHODS: We determined the ACE gene I/D genotype of 2,222 consecutive patients with symptomatic coronary artery disease who underwent stent implantation. The patients with the DD genotype (n = 612) constituted the study population. The primary end point was in-stent restenosis, which was assessed as angiographic restenosis (> or =50% diameter stenosis at six-month follow-up) and clinical restenosis (need for target vessel revascularization due to symptoms or signs of ischemia in the presence of angiographic restenosis over one year after the intervention). RESULTS: Of the 612 patients with the DD genotype, 403 (65.8%) were treated with ACE inhibitors and 209 (34.2%) did not receive ACE inhibitors. The angiographic and clinical restenosis rates were not significantly different between the group treated with ACE inhibitors and the group not receiving ACE inhibitors (p = 0.55). Continuous measures of restenosis, minimal lumen diameter, diameter stenosis, late lumen loss, and loss index were also similar in both groups (p > or = 0.55). In addition, one-year survival free of myocardial infarction was not significantly different between the two groups (p = 0.27). CONCLUSIONS: In contrast to previous reports, our study provides evidence that patients carrying the DD genotype are not exposed to an increased risk of restenosis after stent placement when treated with ACE inhibitors.     

血管紧张素转换酶和血管紧张素受体基因多态性与冠心病的关系

目的　探讨深圳地区冠心病 (CAD)与血管紧张素转换酶 (ACE)基因与血管紧张素 的 1型受体 (AT1R)基因多态性的关系。方法　分别采用 PCR及 PCR- Afl II酶切法 ,检测 89例 CAD患者和 14 8例健康对照的 ACE和AT1R基因型。结果　 CAD组与对照组比较 ,ACE DD基因型频率 (2 4 .7%比 8.1% ,P<0 .0 1)及 D型等位基因频率 (4 4 .4 %比 33.4 % ,P<0 .0 5 )均为升高。 CAD组与对照组 AT1R基因型频率分布无显著性差异 (P>0 .0 5 )。携带 AT1R C等位基因的个体患 CAD的风险与其同时携带 ACE DD基因型无关 (P>0 .0 5 )。结论　深圳地区CAD的发生和发展可能与 ACE基因 I/ D多态性有关 ,而与 AT1R基因 A116 6 C多态性无关     

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.     

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。     

Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35–65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.     

Vascular multimorbidity in patients with a documented coronary artery disease

Atherosclerotic artery disease is a systemic vascular disorder typically involving multiple vascular territories in the same patient. To assess the prevalence and the topographic distribution of non-coronary peripheral artery disease (PAD), cerebrovascular (CVD) and renal artery disease (RAD) in patients with an angiographically confirmed coronary artery disease (CAD) a cross-sectional survey among inpatients admitted for symptoms of CAD was performed. The relationship between CAD and multiterritory vascular disease, and the major risk factors were also assessed. A total of 1855 consecutive patients, mean age 65 +/- 10.6 years (18-92 years), 1184 (63.8%) men and 671 (36.2%) women with an angiographically confirmed CAD were studied. The patients were divided into four age groups: group A < 35 years of age, group B 35 to 54 years, group C 55 to 74 years and group D > or =75 years of age. While 1265 (68.2%) had no evidence of a relevant non-coronary artery disease, in 590 (31.8%) a significant non-coronary artery disease in at least one additional major vascular territory was documented. CAD was most frequently associated with PAD in n = 176 (9.5%) patients. In 22 (1.2%), all four studied vascular territories were significantly diseased. The prevalence of the multi-territory artery disease increased with age: lowest in group A and highest in the group D. However, the data analysis by gender revealed the highest prevalence of CAD associated with PAD and RAD, respectively, in women 35 to 54 years of age. Using the multivariant logistic regression model, type II diabetes was the only major risk factor for a multi-territory expression of atherosclerosis.     

The role of angiotensin converting enzyme genotype in coronary artery ectasia

Coronary artery ectasia (CAE) is characterised by irregular, diffuse, saccular, or fusiform dilatation of the coronary arteries. Although the underlying mechanisms are not fully understood, CAE is considered to be an original form of vascular remodelling in response to atherosclerosis. However, it is not clear why some patients develop CAE while most do not. Experimental data suggest that activation of the renin angiotensin system may lead to an increased inflammatory response in the vessel wall or to an activation of matrix metalloproteinases. In addition, an insertion/deletion (ID) polymorphism of angiotensin converting enzyme (ACE) has been associated with coronary vascular tone and the development of aneurysms. Accordingly, we hypothesised that the gene polymorphism of ACE may be a potential factor influencing the genesis of CAE. We retrospectively evaluated 112 patients who underwent coronary angiography. ACE ID genotype was determined in two groups of patients. Group 1 consisted of 56 patients who were found to have CAE. Group 2 consisted of 56 patients with significant coronary artery disease (CAD) (> 50% stenosis in any of the major epicardial coronary arteries or their branches) but without any evidence of coronary ectasia. Polymerase Chain Reaction (PCR) was used to detect ACE genotype. The ratio of DD genotype was found to be greater in group 1 than group in 2 (39% versus 18%, respectively, P < 0.05). When assessed according to the presence of the I allele, it was greater was greater in group 2 than in group 1 (82.1% versus 60.7%, respectively, P < 0.05). The results indicate that an ACE DD genotype may be a risk factor for CAE.     

The D allele of the angiotensin-converting enzyme gene contributes towards blood LDL-cholesterol levels and the presence of hypertension.

Coronary artery disease is a polygenic disease whose phenotypic manifestation depends on the interaction of the genetic background with a number of environmental factors. Recently, the gene coding for the angiotensin-converting enzyme (ACE) has been characterized and a deletion/insertion (D/I) polymorphism was defined. The prevalence of the three genotypes and their association with coronary artery disease (CAD) differ in different population groups. Mostly, the D allele was found as a significant risk factor for CAD, independently from other risk factors. In the present study, we determined the distribution of ACE alleles (D or I) in a cohort of healthy Israeli men and examined the correlation of the different genotypes with various CAD risk factors. We found LDL cholesterol levels to be highest in the DD genotype group, intermediate in the DI genotype group and lowest in the II genotype group. We also found higher blood pressure levels in subjects bearing the D allele compared to II homozygous subjects. In conclusion, it appears that the genetic influence of the D/I polymorphism on CAD manifests primarily through traditional risk factors.     

血管紧张素转化酶基因插入／缺失多态性与老年糖耐量低减合并冠心病相关性研究

目的：探讨血管紧张素转化酶基因（ACE）多态性与中国汉族老年人糖耐量低减（IGR）及合并冠心病（CAD）的关系。方法：使用多聚合酶链反应方法检测79例糖耐量低减老年人和49例糖耐量正常（NGF）老年对照者的ACE第16内含子中长度为287bp碱基片段的插入／缺失（I／D）情况,结果：IGT组（n=79)和NGT组（n=40)相比,D型等位基因和DD基因型频率升高（P＜0．05,P＜0．005）;IGT合并冠心病组（n=31)和IG非冠心病组（n=48）相比,DD基因型频率升高（P＜均0．005）,结论：ACE多态性和与老年人糖耐量减冠心病相关,IGT和DD基因型是老年冠心病的重要危险因子。     

The association between angiotensin-converting enzyme gene polymorphism and coronary calcification. The Rotterdam Coronary Calcification Study

BACKGROUND: An insertion/deletion (I/D) polymorphism in the gene encoding angiotensin-converting enzyme (ACE) has been associated with serum ACE levels. The association between the ACE I/D polymorphism and coronary heart disease is unclear. Electron-beam-computed tomography (EBT) is a technique to non-invasively quantify the amount of coronary calcification. We investigated the association between the ACE I/D polymorphism and coronary calcification. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects aged 55 years and over. EBT scanning was performed in 2013 participants. Coronary calcification was quantified according to the Agatston score. The ACE I/D polymorphism was available for 1976 subjects. Geometric mean calcium scores in men with the II, ID and DD genotype were 167, 207 and 219, respectively. However, the difference in calcium score (p=0.19 for ID versus II; p=0.15 for DD versus II) and the trend (ptrend=0.17) were not significant. Calcium scores in women with the II, ID and DD genotype were 44, 42 and 36, respectively. There were no significant differences in calcium score (p=0.78 for ID versus II; p=0.29 for DD versus II), neither was the trend (ptrend=0.27). After we stratified on cardiovascular risk factors, no associations were present. CONCLUSION: The present study failed to show an association between the ACE I/D polymorphism and coronary calcification in the general population. Also, no significant associations were present between the ACE I/D polymorphism and coronary calcification in strata of cardiovascular risk factors.     

The platelet Pl(A2) and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction.

Chromosome 17q21-23 harbors genes for platelet glycoprotein IIIa and angiotensin-converting enzyme (ACE), which are polymorphic for alleles Pl(A2) and ACE "D." These alleles have been independently and often associated with ischemic coronary artery disease (CAD). We sought to determine if the Pl(A2) and ACE D polymorphisms were risk factors for recurrent coronary events. In the Cholesterol And Recurrent Events (CARE) trial, 4,159 men and women with documented myocardial infarction (MI) were randomized to receive either placebo or pravastatin, and were followed prospectively for 5 years. Pl(A) and ACE genotypes were determined in 767 patients: 385 cases who had experienced a recurrent primary event (death due to coronary disease or nonfatal MI), and 382 age- and gender-matched controls. In patients receiving placebo, the Pl(A1,A2) genotype conferred a relative risk (RR) of 1.38 (confidence intervals [CI] 1.04 to 1.83; p = 0.028; adjusted RR = 1.32, CI = 0.99 to 1.76; p = 0.058]) for the primary end point. Compared with the placebo group, pravastatin reduced the excess RR of coronary disease death and recurrent MI in the Pl(A1,A2) patient population by 31% (p = 0.06). The ACE D allele appeared to have modestly additive effects on the Pl(A1,A2) risk. Among the Pl(A1,A2) patients, pravastatin had little effect on the risk of recurrent events with the ACE II genotype, but reduced the adjusted RR from 1.42 (placebo) to 0.58 for ACE ID patients, and from 1.56 (placebo) to 0.83 for ACE DD. The Pl(A1,A2) genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin, and the ACE D allele added to this risk. These data suggest that it would be important to perform a larger study to address the potential role of these genotypes in therapeutic decision making.     

Interaction of the ACE D allele and the GNB3 825T allele in myocardial infarction

In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 825T allele of the G-protein ss(3)-subunit gene (GNB3) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D:/I variant affects the renin-angiotensin system hormones that activate G-protein-coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D: allele and the GNB3 825T allele (P<0.001). The odds ratio for MI, associated with the 825T allele, was not increased in the presence of the ACE II genotype (OR 0.5; P=0.09) but was significantly higher in 825T allele carriers with the ACE DI genotype (OR 1.9; P=0.01) and further increased in individuals with the ACE DD genotype (OR 2.4; P=0.02). The highest odds ratio was found in homozygous 825T allele carriers with the ACE DD genotype (OR 7.5; P=0.006). Our data suggest a significant interaction of the GNB3 825T allele with the ACE D allele in MI. These hypothesis-generating data may justify larger prospective studies.     

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.     

血管紧张素转换酶基因I/D多态性及其血清活性与冠心病的关系

目的 :从分子遗传水平探讨血管紧张素转换酶与冠心病的关系及其对冠状动脉病变程度的预测价值。方法 :3 45例患者包括对照患者 95例、心绞痛患者 10 0例及陈旧性心肌梗死患者 15 0例 ,通过两次聚合酶链反应确定血管紧张素转换酶基因型 ,并测定血清血管紧张素转换酶水平。为分析血管紧张素转换酶基因型与冠心病、心肌梗死的相关性 ,将心绞痛患者与陈旧性心肌梗死患者合称冠心病患者 ,对照患者与心绞痛患者合称非心肌梗死患者。结果 :血管紧张素转换酶活性在对照患者、心绞痛患者及心肌梗死患者间无统计学差异。血管紧张素转换酶基因DD、DI和II型的血清血管紧张素转换酶活性有显著性差异 ,经SpearmanRankCorrelation分析 ,血管紧张素转换酶活性与D等位基因数目存在等级相关 ,相关系数 0 2 2 5 ,P <0 0 0 1。血管紧张素转换酶基因型分布在对照患者与冠心病患者、心肌梗死患者与非心肌梗死患者间无显著性差异 ,然而经Logistic回归分析发现 ,在排除其他因素影响下血管紧张素转换酶基因DD型与II型相比 ,对冠心病及心肌梗死的危险性明显增加 ,调整后的OR值分别为 2 2 9及 1 68(P <0 0 5 ) ,提示血管紧张素转换酶基因DD型是冠心病、心肌梗死发生的危险因素。血管紧张素转换酶基因型分布及血清水平均与冠状动     

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism.