D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis]

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.     

ACE基因I/D多态性与冠状动脉支架内再狭窄相关性研究

目的研究冠状动脉内行药物洗脱支架置入术患者,术后支架内再狭窄发生情况与ACE基因I/D多态性的关系。方法所有患者行冠状动脉造影检查,PCR方法测定ACE基因型。根据血管造影结果分为再狭窄组（病变狭窄≥50%）和无再狭窄组（病变狭窄〈50%）。采用SPSS18.0软件比较再狭窄组与无再狭窄组的临床基本特征、冠脉造影资料,以及与ACE基因型的关系。结果此次研究共纳入396名行药物洗脱支架置入术的冠心病患者,支架内再狭窄发生40例,再狭窄率为10.1%。再狭窄组与无再狭窄组的临床基本资料、冠脉造影资料均无显著性差异（P〉0.05）。再狭窄组的ACEDD基因型35.56%、ACEDI基因型16.39%、ACEII基因型3.85%。再狭窄组与ACE基因I/D多态性具有相关性（P〈0.001）。结论冠状动脉内行药物洗脱支架置入术患者术后支架再狭窄发生与ACEDD基因型具有显著相关性。     

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.     

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.     

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.     

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.     

Effect of angiotensin-converting enzyme inhibition on restenosis after coronary stenting

The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a major risk factor for restenosis after coronary stent implantation in selected patients; ACE inhibition may therefore contribute to prevent its occurrence. The effect of oral ACE inhibition at conventional doses was analyzed retrospectively in a series of 897 patients with ischemia who received >or=1 coronary stent on 998 lesions and underwent angiographic follow-up; no exclusion criteria were introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm, respectively (p = 0.0001). During univariate analysis, a negative effect of the drug on restenosis was observed in all subgroups of patients (i.e., hypertensives, diabetics, women, and patients with previous myocardial infarction). Similar effects were observed independently of the ACE gene insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to 2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR 2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38 to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data suggest that the use of conventional oral doses of ACE inhibitors in a "real-world" population who underwent coronary stent implantation increases the incidence of in-stent restenosis. Such a finding does not negate the known clinical benefits of ACE inhibitors, but it may deserve attention when a patient treated with ACE inhibitors becomes a candidate for stent implantation.     

Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene.

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.     

Different impact of deletion polymorphism of gene on the risk of renal and coronary artery disease.

OBJECTIVE: An increased frequency of the angiotensin converting enzyme (ACE) D variant has recently been reported in patients with atheromatous renal artery disease (RAD), whereas controversy exists on the risk of coronary artery disease (CAD) associated with this polymorphism. In spite of the frequent coexistence of RAD and CAD, no studies have specifically compared ACE insertion/deletion (I/D) polymorphism in patients with coronary versus renal artery disease or defined the risk of each disease associated with the D variant. DESIGN: We designed a large case-control study of subjects for whom objective renal or coronary angiographic documentation was available. METHODS AND RESULTS: We analysed ACE I/D genotype and clinical-biochemical data of a total of 942 subjects (123 patients with and 137 without angiographic evidence of RAD, 420 patients with and 262 without angiographic evidence of CAD). Renal (with and without RAD) and coronary patients were similar for most conventional risk factors. There was no difference in DD frequency between CAD and CAD-free patients (38.1 versus 33.6%, NS) and DD homozygosity was not associated with CAD risk (OR = 1.27, 95% CI = 0.82-1.98). In contrast, the DD genotype was more frequent in RAD than in RAD-free patients (54.5 versus 39.4, P < 0.05) and was associated with a 2.25-fold increased risk of RAD in both the univariate and multivariate logistic regression models. Additional predictors of RAD were age and creatinine. In RAD/RAD-free patients with angiographically documented CAD, DD homozygosity was confirmed to be preferentially associated with RAD (P < 0.05). CONCLUSIONS: ACE D variant is preferentially associated with atherosclerotic renal rather than with coronary disease, despite similar exposure to atherogenic noxae. DD homozygosity confers a 2.25-fold increased risk of RAD.     

Polymorphism of the angiotensin-converting enzyme (ACE) and angiotesinogen (AGT) genes and their associations with blood pressure and carotid artery intima media thickness among healthy Finnish young adults--the Cardiovascular Risk in Young Finns Study

The roles of angiotensin converting enzyme (ACE) insertion-deletion (I/D) and angiotensinogen (AGT) m235t polymorphisms in cardiovascular diseases have been investigated extensively during the past decade but results have been inconsistent. A sex-specific association between the ACE I/D polymorphism and systolic blood pressure (BP) was seen among Finnish children and adolescents previously. We investigated if these polymorphisms associate with the BP and carotid artery intima media thickness (IMT) in the same cohort during their adulthood. IMT data were available for 224 ACE I/D genotyped individuals and 202 AGT m235t genotyped individuals. Systolic and diastolic blood pressure values did not differ between ACE and AGT genotypes. Age and BMI adjusted mean IMT was 0.02 (95% CI: -0.05 to 0.02, p=0.33) and 0.03 mm (95% CI: -0.07 to 0.001, p=0.06) lower among the ID and DD genotype groups, respectively, compared to the II genotype group. MT and TT genotype groups had 0.02 mm (95% CI: -0.01 to 0.05, p=0.17) higher and 0.01 mm (95% CI: -0.04 to 0.02, p=0.59) lower mean IMT, respectively, compared to the MM genotype group. We conclude that ACE I/D and AGT m235t polymorphisms are not associated with carotid IMT in healthy young Finnish adults.     

Sex difference in the effect of ACE-DD genotype on the risk of premature myocardial infarction

In this association study the authors compared the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism in females and males with premature myocardial infarction (MI). I/D ACE gene polymorphism was tested in 738 subjects: 302 patients with MI (151 men and 151 women) and 436 healthy subjects (207 men and 229 women). In women the ACE-DD genotype was not associated with MI (OR 1.1, 95% CI 0.6-2.1, p=0.6), whereas the ACE-DD genotype conferred a 2-fold independent risk for MI in men (95% CI=1.2-3.4; p=0.013) after adjustment for cardiovascular risk factors. The authors found evidence for the sex difference in the effect of the ACE-DD genotype on MI risk. The ACE-DD genotype conferred a 2-fold independent risk for premature MI in males.     

Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus erythematosus: a metaanalysis

OBJECTIVE: To explore whether insertion (I) and deletion (D) polymorphisms within intron 16 of the angiotensin-converting enzyme (ACE) gene confer susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). METHODS: We surveyed studies of ACE I/D polymorphism and SLE using Medline and manual searches. We conducted a metaanalysis of the DD genotype (recessive effect), DD and DI genotype (dominant effect), and D allele of the ACE overall and in each ethnic population. We performed a metaanalysis of ACE I/D polymorphism in SLE and LN. RESULTS: Thirteen comparison studies were included in our metaanalysis consisting of 1411 patients with SLE and 1551 controls. We found no association of ACE I/D polymorphism with SLE in the total sample and by ethnic groups. There was a trend for association of the DD genotype (OR 1.212, 95% CI 0.966-1.520, p = 0.097) and the D allele with SLE in Caucasian patients (OR 1.157, 95% CI 0.991-1.349, p = 0.064); however, this was not statistically significant. The metaanalysis also showed no association of the ACE I/D polymorphisms with LN. CONCLUSION: This metaanalysis of 2962 subjects showed there is a lack of association of the ACE I/D polymorphism with SLE and LN.     

Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients

The association between angiotensin-converting enzyme (ACE) genotypes and functional decline in older adults remains controversial. To assess if ACE gene variations influences functional abilities at older age, the present study explored the association between the common ACE insertion/deletion (I/D) polymorphism and disability measured with activities of daily living (ADL) in hospitalized older patients. We analyzed the frequency of the ACE genotypes (I/I, I/D, and D/D) in a population of 2,128 hospitalized older patients divided according to presence or absence of ADL disability. Logistic regression analysis adjusted for possible confounding factors, identified an association between the I/I genotype with ADL disability (OR=1.54, 95% CI 1.04-2.29). This association was significant in men (OR=2.01, 95% CI 1.07-3.78), but not in women (OR=1.36, 95% CI 0.82-2.25). These results suggested a possible role of the ACE polymorphism as a genetic marker for ADL disability in hospitalized older patients.     

The expression of angiotensin-I converting enzyme in human atherosclerotic plaques is not related to the deletion/insertion polymorphism but to the risk of restenosis after coronary interventions

Plasma and tissue concentrations of the angiotensin-I converting enzyme (ACE) have been shown to be associated with the ACE insertion/deletion (I/D) polymorphism. The purpose of this study was to examine the relation of ACE levels in atherosclerotic plaques to the ACE I/D polymorphism and to restenosis after balloon angioplasty and directional atherectomy (DCA). The study included 104 patients who underwent DCA and received angiographic follow-up at 12 to 18 months. The amount of ACE protein in various morphologically defined plaque components (fibrous, atheromatous, and complicated lesions) of the atherectomy specimens was determined by qualitative and semiquantitative immunohistochemistry. ACE levels were related to the ACE genotype, to plaque morphology and to the risk of restenosis. Sequential staining revealed that pathologic ACE overexpression of the atherosclerotic lesions occurred in intimal smooth muscle cells, fibrocytes/fibroblasts and macrophage/foam cells. The ACE content of the whole plaques and of the single plaque components was not associated with the I/D polymorphism, but with restenosis after coronary interventions. In addition, ACE levels in the atherosclerotic lesions correlated with the severity of vessel wall damage. The ACE phenotype might serve as an indicator for the risk of restenosis after coronary interventions.     

The D allele of the angiotensin-converting enzyme insertion/ deletion (I/D) polymorphism is a risk factor for type 2 diabetes in a population-based Japanese sample

The association of the ACE gene I/D polymorphism with type 2 diabetes (DM) was examined in a population-based Japanese sample. A total of 902 individuals (490 females and 412 males, age 58.8 +/- 12.2 yr) from a cohort population (n = 3,706) of the Funagata diabetes study were divided into three groups according to genotype: D/D (n = 104), I/D (n = 436) and I/I (n = 362). Chi-square test and ANOVA were used for association studies and to assess the differences in the traits' values, respectively. More individuals with the genotypes D/D and I/D were diabetic (8.7% and 4.1%, respectively) than those with the genotype I/I (2.8%, p = 0.008 and p = 0.032, respectively). The genotype D/D was a risk factor for DM (relative risk (RR) 3.13, 95% CI 1.31-7.51), and also for DM and IGT (RR 1.78, 95% CI 14-2.76). Multiple logistic regression analysis also showed that the genotypes with the D allele were risk factors for DM and IGT even when adjusting for age, sex, hypertension and serum total cholesterol levels (odds ratio 1.49, 95% CI 1.01-2.21). The D allele of the ACE gene I/D polymorphism is a risk factor for DM.     

Angiotensin-converting enzyme gene polymorphism and common carotid stiffness. The Rotterdam study

The insertion/deletion (I/D) polymorphism of the ACE gene may be involved in structural arterial changes. Aim of the present study was to assess the relationship between the ACE I/D gene and vessel wall stiffness among older adults. The study was conducted within the Rotterdam study, a population-based cohort study including subjects aged 55 years and older. The II, ID and DD genotypes of the ACE gene were determined in all subjects. The distensibility coefficient (10(-3)/kPa) of the carotid artery and the carotid-femoral pulse wave velocity were measured during the third phase of the Rotterdam study (1997-1999) and were used as measure of arterial stiffness. Data on both carotid stiffness and the ACE genotype were available for 3001 participants. After adjustment for age and gender, subjects with the ID and DD genotype had higher carotid stiffness compared to subjects with II genotype (distensibility coefficient (10(-3)/kPa) 10.24 (95% CI, 10.06-10.43), 10.27 (95% CI, 10.02-10.52), 10.65 (95% CI, 10.37-10.93), respectively (ID versus II genotype, P = 0.017), (DD versus II genotype, P = 0.037)). In stratified analyses, the association was strongest in subjects younger than 70 years. No difference was seen for pulse wave velocity among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with higher common carotid stiffness.     

Ace D/I polymorphism and incidence of post-PTCA restenosis: a prospective, angiography-based evaluation

Early restenosis is the major complication of percutaneous transluminal coronary angioplasty (PTCA), occurring in approximately 30% of all initially successful procedures. The D/I polymorphism of the ACE gene, which has variably been reported to represent a risk factor for manifestations of ischemic heart disease, has recently been implicated in the pathophysiology of restenosis after PTCA by some investigators but not by others. All studies conducted thus far involved relatively small sample sizes. We investigated the possible association of ACE D/I genotype and post-PTCA restenosis in a large, prospective sample of patients followed by quantitative coronary angiography. The ACE D/I gene polymorphism was characterized in a cohort of 779 patients, of whom 342 (cases) had developed restenosis (as defined by >50% loss of lumen compared with immediate postprocedure results) at repeat quantitative coronary angiography at 6 months after PTCA. Allele frequencies for the ACE D and I: alleles were 0.58 and 0.42 in cases and 0.58 and 0.42 in control subjects. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and restenosis or degree of lumen loss. The data from this largest study of its kind conducted so far provide no evidence for an association of the ACE D/I allelic polymorphism with incidence of restenosis after PTCA. On the basis of the power of this study, we conclude that in a general population, the ACE D/I polymorphism is not a useful marker to assess risk of post-PTCA restenosis.     

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the risk for restenosis after PTCA

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in about 30% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. We determined the angiotensin I-converting enzyme (ACE) I/D genotype as a possible risk factor for restenosis in 511 consecutive patients who had undergone successful PTCA and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. One hundred sixty patients had restenosis as defined by a greater than 50% progression of residual stenosis of the dilated segment at follow-up angiography. There were significantly more patients with the ACE DD genotype in the restenosis than in the no-restenosis group. This difference did not remain statistically significant in an analysis of covariance that included genetic and clinical variables. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA as well as less residual stenosis immediately after PTCA. We conclude that the ACE DD genotype is not an independent risk factor for restenosis after PTCA.Presented in part at the 41st Annual Congress, International College of Angiology, Sapporo, Japan, July 1999.     

Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases: A study on North Indian patients

Angiotensin-converting enzyme (ACE) is the key enzyme of the renin angiotensin system (RAS) which maintains the blood pressure homeostasis in our body. The association of the ACE insertion/deletion (I/D) polymorphism with essential hypertension has been demonstrated by many studies. The purpose of the present study is to investigate the association of the insertion/deletion polymorphism of the ACE gene with hypertension and additive diseases in North Indian population. In total, 222 hypertensive and 218 normotensive adults participated in this hospital-based study. Anthropometric measures, lipids profiles, blood glucose, and blood pressure (BP) measures were collected from participants. ACE I/D polymorphism was determined by using insertion-specific amplification. The mean ages of study groups were 50.35 ± 12.40 and 47.32 ± 11.94 for cases and controls, respectively. Significant differences were observed in the frequencies of DD, ID, and II genotypes among the hypertensive and normotensive groups which were found to be 29.7%, 38.7%, and 31.5% vs. 53.7%, 23.4%, and 22.9%, respectively. It has been observed that the ACE ID genotype was significantly (p < 0.05) higher in hypertensive subjects, whereas, the DD genotype was significantly (p < 0.05) higher in control subjects. A strong association was found between cardiovascular diseases (CVDs) and ID genotype [p = 0.017, odds ratio (OR) = 3.091, 95% confidence interval (CI) = 1.224–7.807]. ID [p = 0.002, OR = 2.020, 95% CI = 1.281–3.185] and II [p = 0.032, OR = 1.677, 95% CI = 1.044–2.694] genotypes are more prone to diabetes with hypertension. This finding suggests that ACE insertion/deletion polymorphism is associated with hypertension and additive diseases in North Indians.     

血管紧张素转化酶基因多态性对血清血管紧张素转化酶水平及血脂的影响

为探讨血管紧张素转化酶基因多态性对本地人群高血压患者和正常人血清血管紧张素转化酶及血脂水平的影响,采用聚合酶链反应技术,对118例高血压患者和98例正常人的血管紧张素转化酶基因插入/缺失多态性进行分型,并检测血清血管祭张素转化酶活性及血脂含量。结果发现,高血压组血管紧张素转化酶三种基因型(缺失纯合子型、插入纯合子型和杂合子型)及插入/缺失等位基因的频率与正常对照组比较差异无统计学意义(X2=0.468,P=0.791;X2=0.379,P=0.538)。血清血管紧张素转化酶活性在三种基因型之间差异有显著性意义(F=17.107,P=0.000)。高血压组总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)高于正常对照组(P<0.05);高血压组三种基因型之间血脂各指标含量及正常对照组三种基因型之间总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和载脂蛋白B含量差异有显著性意义(P<0.05)。此结果提示,血管紧张素转化酶基因多态性与血清血管肾张素转化酶活性及血脂含量有关,缺失纯合子型高血压患者血清血管紧张素转化酶活性最高且易患高脂血症。